===============================================================================

     As filed with the Securities and Exchange Commission on May 13, 2004

                                               REGISTRATION NO. 333 -

                                  UNITED STATES
                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                 ---------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                    UNDER THE
                             SECURITIES ACT OF 1933

                                 ---------------

                       VERTEX PHARMACEUTICALS INCORPORATED
             (EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

          MASSACHUSETTS                                     04-3039129
  (STATE OR OTHER JURISDICTION                           (I.R.S. EMPLOYER
OF INCORPORATION OR ORGANIZATION)                       IDENTIFICATION NO.)

                               130 WAVERLY STREET
                       CAMBRIDGE, MASSACHUSETTS 01239-4242
          (ADDRESS, INCLUDING ZIP CODE, OF PRINCIPAL EXECUTIVE OFFICES)

                          EMPLOYEE STOCK PURCHASE PLAN
                            (FULL TITLE OF THE PLAN)

                             JOSHUA S. BOGER, PH.D.
                      CHAIRMAN AND CHIEF EXECUTIVE OFFICER
                       VERTEX PHARMACEUTICALS INCORPORATED
                               130 WAVERLY STREET
                       CAMBRIDGE, MASSACHUSETTS 02139-4242
                                 (617) 444-6100
                 (NAME, ADDRESS AND TELEPHONE NUMBER, INCLUDING
                        AREA CODE, OF AGENT FOR SERVICE)

                                 ---------------




                                                       CALCULATION OF REGISTRATION FEE
=============================== =================== ===================== =========================== ===========================
                                                          Proposed                 Proposed
          Title of                 Amount to be            Maximum                  Maximum
 Securities to be Registered       Registered(1)       Offering Price              Aggregate                   Amount of
                                                        Per Share (2)         Offering Price (2)           Registration Fee
------------------------------- ------------------- --------------------- --------------------------- ---------------------------
                                                                                          
Common Stock, $.01 par value      1,500,000 shares         $8.82                 $13,230,000                    $1,677
=============================== =================== ===================== =========================== ===========================
 Rights to purchase Series A           (3)                  (3)                      (3)                         None
     Junior Participating
       Preferred Stock
=============================== =================== ===================== =========================== ===========================



(1)  The number of shares of common stock, par value $.01 per share ("Common
     Stock"), stated above consists of the aggregate number of shares which may
     be sold under the Employee Stock Purchase Plan (the "Plan"). The maximum
     number of shares which may be sold upon the exercise of options granted
     under the Plan are subject to adjustment in accordance with certain
     anti-dilution and other provisions of the Plan. Accordingly, pursuant to
     Rule 416 under the Securities Act of 1933, as amended (the "Securities
     Act"), this Registration Statement covers, in addition to the number of
     shares stated above, an indeterminate number of shares which may be subject
     to grant or otherwise issuable after the operation of any such
     anti-dilution and other provisions.
(2)  This calculation is made solely for the purpose of determining the
     registration fee pursuant to the provisions of Rule 457(c) and (h) under
     the Securities Act as follows: because the purchase price of the shares
     is not yet known, the fee is calculated on the basis of the average of the
     high and low sale prices per share of the Common Stock on the Nasdaq Stock
     Market as of a date (May 7, 2004) within five business days prior to
     filing this Registration Statement.
(3)  No separate consideration will be received for the Rights.

===============================================================================




                                EXPLANATORY NOTE

         In accordance with the instructional Note to Part I of Form S-8 as
promulgated by the Securities and Exchange Commission, the information specified
by Part I of Form S-8 has been omitted from this Registration Statement on Form
S-8 for offers of Common Stock pursuant to the Plan.




                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT


ITEM 3.  INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE.
--------------------------------------------------------

         The following documents filed by the Registrant with the Commission are
incorporated herein by reference:

         (a) The Registrant's Annual Report on Form 10-K for the fiscal year
ended December 31, 2003 (filing date March 15, 2004).

         (b) The Registrant's Quarterly Report on Form 10-Q for the fiscal
quarter ended March 31, 2004 (filing date May 10, 2004).

         (c) The following Current Reports of the Registrant on Form 8-K,
except that information furnished under either Item 9 or Item 12 is not
incorporated by reference:

             (i)   Current Report on Form 8-K filed February 3, 2004

             (ii)  Current Report on Form 8-K filed February 10, 2004

             (iii) Current Report on Form 8-K filed February 13, 2004

             (iv)  Current Report on Form 8-K filed February 23, 2004

             (v)   Current Report on Form 8-K filed May 10, 2004

         (d) The description of the Common Stock contained in the Registrant's
Registration Statement on Form S-4 (Reg. No. 333-61480) filed under the
Securities Act of 1933, including any amendment or report filed for the purpose
of updating such description.

         (e) The description of the Rights under the Registrant's Rights
Agreement (which are currently transferred with the Registrant's Common Stock)
contained in the Registrant's Registration Statement on Form S-4 (No. 333-61480)
filed under the Securities Act of 1933, including any amendment or report filed
for the purpose of updating such description.

         All reports and other documents filed by the Registrant after the date
hereof pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior
to the filing of a post-effective amendment which indicates that all securities
offered hereby have been sold or which deregisters all securities then remaining
unsold, shall be deemed to be incorporated by reference herein and to be part
hereof from the date of filing of such reports and documents.

ITEM 4.  DESCRIPTION OF SECURITIES.
----------------------------------

         Not applicable.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.
-----------------------------------------------

         Not applicable.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.
--------------------------------------------------

         Part D of Article 6 of the Restated Articles of Organization of the
Registrant provides that no director of the Registrant shall be personally
liable to the Registrant or its stockholders for monetary damages for breach of
fiduciary duty as a director. Such paragraph provides further, however, that, to
the extent provided by applicable law, it will not eliminate or limit the
liability of a director (i) for any breach of the director's duty of loyalty to
the Registrant or its stockholders, (ii) for acts or omissions not in good faith
or which involve intentional misconduct or a knowing violation of law, (iii) for
distributions made in violation of the Registrant's Restated Articles of
Organization or which are made when the Registrant is insolvent or which renders
it insolvent, (iv) for loans made to officers or directors of the Registrant
which are not repaid if the director has voted for such loans and they have not
been approved or ratified as loans


                                       1



reasonably expected to benefit the Registrant, by a majority of directors who
are not recipients of such loans or the holders of a majority of voting shares,
which holders are not recipients of such loans, and (v) for any transactions
from which the director derived an improper personal benefit.

         Article V of the Registrant's By-laws provides that the Registrant
shall indemnify each of its directors and officers (including persons who serve
at the Registrant's request as a director, officer or trustee of another
organization in which the Registrant has any interest, direct or indirect, as a
stockholder, creditor or otherwise or who serve at the Registrant's request in
any capacity with respect to any employee benefit plan) against all liabilities
and expenses, including amounts paid in satisfaction of judgments, in compromise
or as fines and penalties and counsel fees reasonably incurred by such directors
or officer in connection with the defense or disposition of any action, suit or
other proceeding, whether civil or criminal, in which such director or officer
may be involved or with which such person may be threatened, while in office or
thereafter, by reason of such person's being or having been such a director,
officer or trustee, except with respect to any matter as to which such director
or officer shall have been adjudicated in any proceeding not to have acted in
good faith in the reasonable belief that such director's or officer's action was
in the best interest of the Registrant or, to the extent that such matter
relates to service with respect to an employee benefit plan, in the best
interest of the participants or beneficiaries of such employee benefit plan.

         As to any matter disposed of by a compromise payment by any such
person, pursuant to a consent decree or otherwise, Article V of the Registrant's
By-laws provides that no indemnification shall be provided to such person for
such payment or for any other expenses unless such compromise has been approved
as in the best interest of the Registrant, after notice that it involves such
indemnification (i) by a disinterested majority of the directors then in office,
(ii) by a majority of the disinterested directors then in office, provided there
has been obtained an opinion in writing of independent legal counsel to the
effect that such director or officer appears to have acted in good faith in the
reasonable belief that such person's action was in the best interest of the
Registrant, or (iii) by the holders of a majority of the outstanding stock at
the time entitled to vote for directors, voting as a single class, exclusive of
any stock owned by any interested director or officer.

         Article V of the Registrant's By-laws provides that expenses, including
counsel fees, reasonably incurred by any director or officer in connection with
the defense or disposition of any such action, suit or other proceeding may be
paid from time to time by the Registrant at the discretion of a majority of the
disinterested directors then in office, in advance of the final disposition
thereof, upon receipt of an undertaking by such director or officer to repay the
Registrant the amounts so paid if it is ultimately determined that
indemnification for such expenses is not authorized under Article V of the
By-laws, which undertaking may be accepted by the Registrant without reference
to the financial ability of such director or officer to make repayment.

         Article V of the Registrant's By-laws gives the Board of Directors of
the Registrant the power to authorize the purchase and maintenance of insurance,
in such amounts as the Board of Directors may from time to time deem
appropriate, on behalf of any person who is or was a director, officer or agent
of the Registrant, or who is or was serving at the request of the Registrant as
a director, officer or agent of another organization in which the Registrant has
any interest, direct or indirect, as a shareholder, creditor or otherwise, or
with respect to any employee benefit plan, against any liability incurred by
such person in any such capacity, or arising out of such person's status as such
agent, whether or not such person is entitled to indemnification by the
Registrant pursuant to Article V or otherwise and whether or not the Registrant
would have the power to indemnify the person against such liability.


                                       2



         Section 13(b)(1 1/2) of the Massachusetts Business Corporation Law,
Chapter 156B of the General Laws of Massachusetts (the "MBCL") authorizes the
provisions, described above, contained in Part D of Article 6 of the Restated
Articles of Organization of the Registrant.

         Section 67 of the MBCL authorizes the provisions, described above,
contained in Article V of the By-laws of the Registrant.

         Section 65 of the MBCL provides that performance by a director, officer
or incorporator of such person's duties in good faith and in a manner such
person reasonably believes to be in the best interest of the corporation, and
with such care as an ordinary prudent person in a like position would use under
similar circumstances, shall be a complete defense to any claim asserted against
such director, officer or incorporator, except as otherwise expressly provided
by statute, by reason of such person's being or having been a director, officer
or incorporator of the corporation.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.
--------------------------------------------

         Not applicable.

ITEM 8.  EXHIBITS.
-----------------

         (4.1)    Specimen Common Stock Certificate (filed as Exhibit 4.1 to
                  Registrant's Registration Statement on Form S-1, as amended,
                  No. 33-40966, and incorporated herein by reference).

         (4.2)    Restated Articles of Organization of the Registrant (filed as
                  Exhibit 3.1 to Registrant's Registration Statement on Form
                  S-4, as amended, No. 333-61480, and incorporated herein by
                  reference).

         (4.3)    By-Laws of the Registrant, as amended and restated (filed as
                  Exhibit 3.5 to Registrant's Registration Statement on Form
                  S-4, as amended, No. 333-61480, and incorporated herein by
                  reference).

         (4.4)    Stockholder Rights Plan (filed as Exhibit 4.2 to Registrant's
                  Registration Statement on Form S-1, as amended, No. 33-40966,
                  and incorporated herein by reference).

         (4.5)    First Amendment to Rights Agreement dated as of February 21,
                  1997 (filed as Exhibit 4.3 to Registrant's 1996 Annual Report
                  on Form 10-K, file No. 000-19319, and incorporated herein by
                  reference).

         (4.6)    Second Amendment to Rights Agreement dated as of June 30, 2001
                  (filed as Exhibit 4.4 to Registrant's Quarterly Report on Form
                  10-Q for the quarter ended June 30, 2001, file No. 000-19319,
                  and incorporated herein by reference).

         (5)      Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
                  as to the legality of shares being registered.

         (23.1)   Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
                  (included in opinion of counsel filed as Exhibit 5).

         (23.2)   Consent of Independent Accountants, PricewaterhouseCoopers
                  LLP.


                                       3




         (24)     Power of Attorney to file future amendments (set forth on the
                  signature page of this Registration Statement).

         (99.1)   Employee Stock Purchase Plan, Amended and Restated as of
                  May 6, 2004.

ITEM 9.  UNDERTAKINGS.
---------------------

(a)      The undersigned Registrant hereby undertakes:

         (1) To file, during any period in which offers or sales are being made,
         a post-effective amendment to this Registration Statement:

                   (i) To include any prospectus required by Section 10(a)(3) of
              the Securities Act of 1933;

                   (ii) To reflect in the prospectus any facts or events arising
              after the effective date of the Registration Statement (or the
              most recent post-effective amendment thereof) which, individually
              or in the aggregate, represents a fundamental change in the
              information set forth in the Registration Statement.
              Notwithstanding the foregoing, any increase or decrease in volume
              of securities offered (if the total dollar value of securities
              offered would not exceed that which was registered) and any
              deviation from the low or high end of the estimated maximum
              offering range may be reflected in the form of prospectus filed
              with the Commission pursuant to Rule 424(b) if, in the aggregate,
              the changes in volume and price represent no more than a 20%
              change in the maximum aggregate offering price set forth in the
              "Calculation of Registration Fee" table in the effective
              Registration Statement;

                   (iii) To include any material information with respect to the
              plan of distribution not previously disclosed in the Registration
              Statement or any material change to such information in the
              Registration Statement;

              PROVIDED, HOWEVER, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
         apply if the Registration Statement is on Form S-3, Form S-8 or Form
         F-3, and the information required to be included in a post-effective
         amendment by those paragraphs is contained in periodic reports filed
         with or furnished to the Commission by the Registrant pursuant to
         Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that
         are incorporated by reference in this Registration Statement.

         (2) That, for the purpose of determining any liability under the
         Securities Act of 1933, each such post-effective amendment shall be
         deemed to be a new registration statement relating to the securities
         offered therein, and the offering of such securities at that time shall
         be deemed to be the initial bona fide offering thereof.

         (3) To remove from registration by means of a post-effective amendment
         any of the securities being registered which remain unsold at the
         termination of the offering.


                                       4



(b)  The undersigned Registrant hereby undertakes that, for purposes of
     determining any liability under the Securities Act of 1933, each filing of
     the Registrant's annual report pursuant to Section 13(a) or Section 15(d)
     of the Securities Exchange Act of 1934 that is incorporated by reference in
     this Registration Statement shall be deemed to be a new registration
     statement relating to the securities offered therein, and the offering of
     such securities at that time shall be deemed to be the initial bona fide
     offering thereof.

(c)  Insofar as indemnification for liabilities arising under the Securities Act
     of 1933 may be permitted to directors, officers and controlling persons of
     the Registrant pursuant to the foregoing provisions, or otherwise, the
     Registrant has been advised that in the opinion of the Securities and
     Exchange Commission such indemnification is against public policy as
     expressed in the Act and is, therefore, unenforceable. In the event that a
     claim for indemnification against such liabilities (other than the payment
     by the Registrant of expenses incurred or paid by a director, officer or
     controlling person of the Registrant in the successful defense of any
     action, suit or proceeding) is asserted by such director, officer or
     controlling person in connection with the securities being registered, the
     Registrant will, unless in the opinion of its counsel the matter has been
     settled by controlling precedent, submit to a court of appropriate
     jurisdiction the question whether such indemnification by it is against
     public policy as expressed in the Act and will be governed by the final
     adjudication of such issue.


                                       5



                                   SIGNATURES

         THE REGISTRANT. Pursuant to the requirements of the Securities Act of
1933, the Registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in Cambridge, Massachusetts on May 13, 2004.


                                      VERTEX PHARMACEUTICALS INCORPORATED


                                      By /S/ JOSHUA S. BOGER
                                         ------------------------------------
                                         JOSHUA S. BOGER
                                         CHIEF EXECUTIVE OFFICER

         Each person whose signature appears below constitutes and appoints
Joshua S. Boger and Valerie L. Andrews, and each of them singly, his/her true
and lawful attorneys-in-fact and agents, with full power of substitution and
resubstitution in each of them singly, for him/her and in his/her name, place
and stead, and in any and all capacities, to sign any and all amendments
(including post-effective amendments) to this Registration Statement on Form S-8
of Vertex Pharmaceuticals Incorporated, and to file the same, with all exhibits
thereto and other documents in connection therewith, with the Securities and
Exchange Commission, granting to the attorneys-in-fact and agents, and each of
them, full power and authority to do and perform each and every act and thing
requisite or necessary to be done in or about the premises, as full to all
intents and purposes as he/she might or could do in person, hereby ratifying and
confirming all that the attorneys-in-fact and agents or any of each of them or
their substitute may lawfully do or cause to be done by virtue hereof.

         Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.




SIGNATURE                                            TITLE                              DATE
                                                                        

/S/ JOSHUA S. BOGER                          Director , Chairman                May 13, 2004
------------------------------------         and Chief Executive Officer
Joshua S. Boger                              (principal executive officer)


/S/ IAN F. SMITH                             Chief Financial Officer            May 13, 2004
------------------------------------         (principal financial officer)
    Ian F. Smith


/S/ JOHANNA MESSINA POWER                    Controller                         May 13, 2004
---------------------------                  (principal accounting officer)
    Johanna Messina Power


                                       6



/S/ ERIC S. BRANDT                           Director                           May 13, 2004
---------------------------
    Eric S. Brandt

/S/ ROGER W. BRIMBLECOMBE                    Director                           May 13, 2004
---------------------------
    Roger W. Brimblecombe

/S/ STUART J. COLLINSON                      Director                           May 13, 2004
------------------------------------
    Stuart J. Collinson

/S/ JOHN F. NIBLACK                          Director                           May 13, 2004
------------------------------------
    John F. Niblack

/S/ BRUCE I. SACHS                           Director                           May 13, 2004
------------------------------------
    Bruce I. Sachs

/S/ CHARLES A. SANDERS                       Director                           May 13, 2004
------------------------------------
    Charles A. Sanders

/S/ EVE E. SLATER                            Director                           May 13, 2004
------------------------------------
    Eve E. Slater

/S/ ELAINE S. ULLIAN                         Director                           May 13, 2004
------------------------------------
    Elaine S. Ullian




                                       7



                      VERTEX PHARMACEUTICALS INCORPORATED
                          INDEX TO EXHIBITS FILED WITH
                        FORM S-8 REGISTRATION STATEMENT


EXHIBIT
NUMBER                 DESCRIPTION

(4.1)             Specimen Common Stock Certificate (filed as Exhibit 4.1 to
                  Registrant's Registration Statement on Form S-1, as amended,
                  No. 33-40966, and incorporated herein by reference).

(4.2)             Restated Articles of Organization of the Registrant (filed as
                  Exhibit 3.1 to Registrant's Registration Statement on Form
                  S-4, as amended, No. 333-61480, and incorporated herein by
                  reference).

(4.3)             By-Laws of the Registrant, as amended and restated (filed as
                  Exhibit 3.5 to Registrant's Registration Statement on Form
                  S-4, as amended, No. 333-61480, and incorporated herein by
                  reference).

(4.4)             Stockholder Rights Plan (filed as Exhibit 4.2 to Registrant's
                  Registration Statement on Form S-1, as amended, No. 33-40966,
                  and incorporated herein by reference).

(4.5)             First Amendment to Rights Agreement dated as of February 21,
                  1997 (filed as Exhibit 4.3 to Registrant's 1996 Annual Report
                  on Form 10-K, file No. 000-19319, and incorporated herein by
                  reference).

(4.6)             Second Amendment to Rights Agreement dated as of June 30, 2001
                  (filed as Exhibit 4.4 to Registrant's Quarterly Report on Form
                  10-Q for the quarter ended June 30, 2001, file No. 000-19319,
                  and incorporated herein by reference).

(5)               Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
                  as to the legality of shares being registered.

(23.1)            Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
                  (included in opinion of counsel filed as Exhibit 5).

(23.2)            Consent of Independent Accountants, PricewaterhouseCoopers
                  LLP.

(24)              Power of Attorney to file future amendments (set forth on the
                  signature page of this Registration Statement).

(99.1)            Employee Stock Purchase Plan, Amended and Restated as of
                  May 6, 2004.


                                       8