THIRD SUPPLEMENTAL INDENTURE

Exhibit 4.1

EXECUTION COPY

HUMANA INC.,

Issuer

THE BANK OF NEW YORK TRUST COMPANY, N.A.,

Trustee

THIRD SUPPLEMENTAL INDENTURE

Dated as of June 5, 2008

7.20% Senior Notes due 2018

Supplemental to Indenture dated as of August 5, 2003

THIS THIRD SUPPLEMENTAL INDENTURE (the “Third Supplemental Indenture”) is made the 5th day of June, 2008, between HUMANA INC., a corporation duly incorporated and existing under the laws of Delaware and having its principal executive office at 500 West Main Street, Louisville, Kentucky 40202 (hereinafter called “the Company”), and THE BANK OF NEW YORK TRUST COMPANY, N.A. (as successor to The Bank of New York), a national banking association, as Trustee (hereinafter called the “Trustee”).

RECITALS OF THE COMPANY

WHEREAS, the Company entered into an Indenture, dated as of August 5, 2003 with the Trustee (the “Original Indenture,” and together with this Third Supplemental Indenture, referred to herein as the “Indenture”) (all capitalized terms used in this Third Supplemental Indenture and not otherwise defined herein have the meanings assigned to such terms in the Original Indenture), for the purposes of issuing its Securities, evidencing its senior unsecured indebtedness, unlimited as to principal amount, to bear such rates of interest, to mature at such time or times, to be issued in one or more series and to have such other provisions as authorized by or pursuant to the authority granted in one or more resolutions of the Board of Directors of the Company; and

WHEREAS, Section 901 of the Original Indenture provides that without the consent of the Holders of the Securities of any series issued under the Original Indenture, the Company, when authorized by a Board Resolution, and the Trustee may, in certain circumstances, enter into one or more indentures supplemental to the Original Indenture; and

WHEREAS, the Company proposes to issue a series of Securities designated as its 7.20% Senior Notes due 2018, the terms of which shall be set forth in, or determined in the manner provided in, an Officers’ Certificate of the Company as provided in Section 301 of the Original Indenture (such senior notes being referred to herein as the “2018 Senior Notes” and all references to Securities in the Original Indenture shall be deemed to refer also to the 2018 Senior Notes unless the context otherwise provides); and

WHEREAS, the entry into this Third Supplemental Indenture by the parties hereto is in all respect authorized by the provisions of the Original Indenture; and

WHEREAS, all conditions necessary to authorize the execution and delivery of this Third Supplemental Indenture and to make it a valid and binding obligation of the Company have been done or performed; and

NOW, THEREFORE, THIS THIRD SUPPLEMENTAL INDENTURE WITNESSETH:

For and in consideration of the promises and the purchase of the 2018 Senior Notes by the Holders thereof, it is mutually covenanted and agreed, for the equal and proportionate benefit of all Holders of the 2018 Senior Notes, as follows:

Section 1. The Original Indenture is hereby amended solely with respect to the 2018 Senior Notes as follows:

“Change of Control” means the occurrence of any one of the following: (1) the direct or indirect sale, lease, transfer, conveyance or other disposition (other than by way of merger or consolidation), in one or a series of related transactions, of all or substantially all of the Company’s assets and its subsidiaries taken as a whole to any Person other than to the Company or a Subsidiary; (2) the consummation of any transaction (including without limitation, any merger or consolidation) the result of which is that any Person becomes the “beneficial owner” (as defined in Rules 13d-3 and 13d-5 under the Exchange Act), directly or indirectly, of more than 50% of the outstanding Voting Stock of the Company or the Voting Stock of any Parent Company (as defined below) or other Voting Stock into which the Voting Stock of the Company or the Voting Stock of any Parent Company is reclassified, consolidated, exchanged or changed, measured by voting power rather than number of shares; (3) the Company or any Parent Company consolidates with, or merges with or into, any Person, or any Person consolidates with, or merges with or into, the Company or any Parent Company, in any such event pursuant to a transaction in which any of the outstanding Voting Stock of the Company, the Voting Stock of such Parent Company or the Voting Stock of such other Person is converted into or exchanged for cash, securities or other property, other than any such transaction where the shares of the Voting Stock of the Company or the Voting Stock of such Parent Company outstanding immediately prior to such transaction constitute, or are converted into or exchanged for, a majority of the Voting Stock of the surviving Person or any Parent Company of the surviving Person immediately after giving effect to such transaction; (4) the first day on which the majority of the members of the Company’s Board of Directors or the board of directors of any Parent Company cease to be Continuing Directors; or (5) the adoption of a plan relating to the liquidation or dissolution of the Company. Notwithstanding the foregoing, a transaction will not be deemed to involve a Change of Control under clause (2) above if (i) the Company becomes a subsidiary of a Parent Company and (ii) the holders of the Voting Stock of the Company or the Voting Stock of any Parent Company immediately prior to such transaction hold at least a majority of the Voting Stock of such Parent Company immediately following such transaction; provided that any series of related transactions shall be treated as a single transaction. The term “Person,” solely as used in this definition, has the meaning given thereto in Section 13(d)(3) of the Exchange Act.

“Change of Control Triggering Event” means the occurrence of both a Change of Control and a related Rating Event.

“Common Stock” means, with respect to any Principal Subsidiary, Capital Stock of any class, however designated, except Capital Stock which is non-participating beyond fixed dividend and liquidation preferences and the holders of which have either no voting rights or limited voting rights entitling them, only in the case of certain contingencies, to elect less than a majority of the directors (or persons

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performing similar functions) of such Principal Subsidiary, and also includes securities of any class, however designated, which are convertible into Common Stock.

“Continuing Director” means, as of any date of determination, any member of the Company’s Board of Directors who:

(1) was a member of the Board of Directors on the Issue Date; or

(2) was nominated for election, elected or appointed to the Board of Directors with the approval of a majority of the Continuing Directors who were members of the Board of Directors at the time of such nomination, election or appointment.

“Indebtedness” means, with respect to any Person (without duplication):

(1) any liability of that Person (A) for borrowed money, or under any reimbursement obligation relating to a letter of credit or similar instrument; (B) evidenced by a bond, note, debenture or similar instrument; (C) to pay the deferred purchase price of property or services, except trade accounts payable arising in the ordinary course of business; or (D) for the payment of money relating to any obligations under any capital lease of real or personal property which has been recorded as a capitalized lease obligation;

(2) any liability of others described in the preceding clause (1) that the Person has guaranteed or that is otherwise its legal liability or which is secured by a lien on that Person’s Property; and

(3) any amendment, supplement, modification, deferral, renewal, extension or refunding of any liability of the types referred to in clauses (1) or (2) above.

“Investment Grade” means a rating of Baa3 or better by Moody’s (or its equivalent under any successor rating category) and a rating of BBB- or better by Standard & Poor’s (or its equivalent under any successor rating category).

“Issue Date” means the first date on which 2018 Senior Notes are issued, which shall be June 5, 2008.

“Moody’s” means Moody’s Investors Services, Inc., or any successor thereto.

“Parent Company” means any holding company that, directly or indirectly, owns 100% of the Voting Stock of the Company.

“Principal Subsidiary” means a consolidated subsidiary of the Company that, as of the relevant time of determination, is a “significant subsidiary” as defined under Rule 405 under the Securities Act of 1933, as amended (as that Rule is in effect on June 3, 2008, without giving effect to any further amendment of that Rule).

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“Rating Agency” means:

(1) each of Moody’s and Standard & Poor’s, and

(2) if either or both of Moody’s or Standard & Poor’s ceases to rate the 2018 Senior Notes or fails to make a rating of the 2018 Senior Notes publicly available for reasons outside of the Company’s control, a Substitute Rating Agency in lieu thereof.

“Rating Event” means (i) the rating of the 2018 Senior Notes is lowered by both Rating Agencies during the related Trigger Period and (ii) the 2018 Senior Notes are rated below an Investment Grade rating by both Rating Agencies on any day during such Trigger Period. If either Rating Agency is not providing a rating of the 2018 Senior Notes on any day during such Trigger Period for any reason, the rating of such Rating Agency shall be deemed to be below Investment Grade on such day and such Rating Agency will be deemed to have lowered its rating of the 2018 Senior Notes during the Trigger Period.

“Standard & Poor’s” means Standard & Poor’s Rating Services, a division of The McGraw Hill Companies, or any successor thereto.

“Substitute Rating Agency” means a “nationally recognized statistical rating organization” within the meaning of Rule 15c3-1(c)(2)(vi)(F) under the Exchange Act, selected by the Company (as certified by a resolution of the Board of Directors and reasonably acceptable to the Trustee) as a replacement agency for Moody’s or Standard & Poor’s, or both of them, as the case may be.

“Trigger Period” means the period commencing on the earlier of the first public notice of (a) the occurrence of a Change of Control or (b) the Company’s intention to effect a Change of Control and ending 60 days following consummation of such Change of Control (which period shall be extended so long as the rating of the 2018 Senior Notes is under publicly announced consideration for a possible downgrade by either of the Rating Agencies).

“Voting Stock” means, with respect to any Person as of any date, the Capital Stock of such Person that is at the time entitled to vote generally in the election of the board of directors (or other analogous managing body) of such Person.

“Notice of Default” has the meaning specified in Sections 501(3) and 501(4).

(2) the Company by such Trustee or by any Holder shall be sufficient for every purpose hereunder (except as provided in paragraphs (3) and (4) of Section 501) if furnished in writing and mailed, first class postage prepaid, addressed to it, to the attention of the Chief Financial Officer, at the address of its principal office specified in the first paragraph of this instrument or at any other address previously furnished in writing to such Trustee by the Company, or if sent by facsimile transmission, to a facsimile number provided to the Trustee by the Company, with a copy mailed, first class postage prepaid, to the Company addressed to it as provided above.

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Section 314. Interest Rate Adjustment .

Interest on the 2018 Senior Notes shall be subject to adjustment as provided in this Section 314.

(a) If the rating from Moody’s or any Substitute Rating Agency thereof of the 2018 Senior Notes is decreased to a rating set forth in the table in this Section 314(a), the interest rate on 2018 Senior Notes shall increase from the interest rate payable on the 2018 Senior Notes on the Issue Date by the percentage points set forth opposite that rating:

(b) If the rating from Standard & Poor’s or any Substitute Rating Agency thereof of the 2018 Senior Notes is decreased to a rating set forth in the table in this Section 314(b), the interest rate on the 2018 Senior Notes shall increase from the interest rate payable on the 2018 Senior Notes on the Issue Date by the percentage points set forth opposite that rating:

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(c) If at any time the interest rate on the 2018 Senior Notes has been adjusted upward pursuant to Section 314(a) or 314(b) and either Moody’s or Standard & Poor’s (or, in either case, a Substitute Rating Agency thereof), as the case may be, subsequently increases its rating of the 2018 Senior Notes to any of the ratings set forth in the table in either Section 314(a) or 314(b), as applicable, the interest rate on the 2018 Senior Notes shall be decreased such that the interest rate for the 2018 Senior Notes equals the interest rate payable on the 2018 Senior Notes on the Issue Date plus the applicable percentage points set forth opposite the ratings in the tables in either 314(a) or 314(b), as applicable, in effect immediately following the increase.

(d) If Moody’s or any Substitute Rating Agency thereof subsequently increases its rating of the 2018 Senior Notes to Baa3 (or its equivalent, in the case of a Substitute