The Twenty-fifth Amendment (Amendment XXV) to the United States Constitution addresses issues related to presidential succession and disability.

It clarifies that the vice president becomes president if the president dies, resigns, or is removed from office by impeachment. It also establishes the procedure for filling a vacancy in the office of the vice president. Additionally, the amendment provides for the temporary transfer of the president's powers and duties to the vice president, either on the president's initiative alone or on the initiative of the vice president together with a majority of the president's cabinet. In either case, the vice president becomes the acting president until the president's powers and duties are restored.

The amendment was submitted to the states on July 6, 1965, by the 89th Congress, and was adopted on February 10, 1967, the day the requisite number of states (38) ratified it.

Section 1 clarifies that in the enumerated situations the vice president becomes president, instead of merely assuming the powers and duties of the presidency as acting president. It operates automatically, without needing to be explicitly invoked.

Section 2 provides a mechanism for filling a vacancy in the vice presidency. Before the Twenty-fifth Amendment, a vice-presidential vacancy continued until a new vice president took office at the start of the next presidential term; the vice presidency had become vacant several times due to death, resignation, or succession to the presidency, and these vacancies had often lasted several years.

Section 3 allows the president to voluntarily transfer presidential authority to the vice president (for example, in anticipation of a medical procedure) by declaring in writing his inability to discharge the presidency's powers and duties. The vice president then assumes those powers and duties as acting president. The vice president does not become president; the president remains in office without authority. The president regains those powers and duties upon declaring in writing his ability to discharge them.

Section 4 addresses the case of a president who cannot discharge the powers and duties of the presidency but also cannot, or does not, execute the voluntary declaration contemplated by Section 3. It allows the vice president, together with a "majority of either the principal officers of the executive departments or of such other body as Congress may by law provide", to issue a written declaration that the president is unable to discharge his duties. When such a declaration is sent to Congress, the vice president immediately becomes acting president, while (as with Section 3) the president remains in office, temporarily divested of authority.

John Feerick, the principal draftsman of the amendment, writes that Congress deliberately left the terms unable and inability undefined "since cases of inability could take various forms not neatly fitting into [a rigid] definition ... The debates surrounding the Twenty-fifth Amendment indicate that [those terms] are intended to cover all cases in which some condition or circumstance prevents the President from discharging his powers and duties".  A survey of scholarship on the amendment found

no specific threshold—medical or otherwise—for the "inability" contemplated in Section 4. The framers specifically rejected any definition of the term, prioritizing flexibility. Those implementing Section 4 should focus on whether—in an objective sense taking all of the circumstances into account—the President is "unable to discharge the powers and duties" of the office. The amendment does not require that any particular type or amount of evidence be submitted to determine that the President is unable to perform his duties. While the framers did imagine that medical evidence would be helpful to the determination of whether the President is unable, neither medical expertise nor diagnosis is required for a determination of inability ... To be sure, foremost in [the minds of the framers] was a physical or mental impairment. But the text of Section 4 sets forth a flexible standard intentionally designed to apply to a wide variety of unforeseen emergencies.

Among potential examples of such unforeseen emergencies, legal scholars have listed kidnapping of the president and "political emergencies" such as impeachment. Traits such as unpopularity, incompetence, impeachable conduct, poor judgment, or laziness might not in themselves constitute inability, but should such traits "rise to a level where they prevented the President from carrying out his or her constitutional duties, they still might constitute an inability, even in the absence of a formal medical diagnosis." In addition, a president who already manifested disabling traits at the time he was elected is not thereby immunized from a declaration of inability.

The "principal officers of the executive department[s]" are the 15 Cabinet members enumerated in the United States Code at 5 U.S.C. § 101:

Acting secretaries can participate in issuing the declaration.

If the president subsequently issues a declaration claiming to be able, then a four-day period begins during which the vice president remains acting president. If, by the end of this period, the vice president and a majority of the "principal officers" have not issued a second declaration of the president's inability, the president resumes his powers and duties; but if they do issue a second declaration within the four days, then the vice president remains acting president while Congress considers the matter. Then, if within 21 days the Senate and the House determine, each by a two-thirds vote, that the president is unable, the vice president continues as acting president; otherwise the president resumes his powers and duties.

Section 4's requirement of a two-thirds vote in both the House and the Senate is stricter than the Constitution's requirement for impeachment and removal of the president for "high crimes and misdemeanors"—a majority of the House followed by two-thirds of the Senate. In addition, an impeached president retains his authority unless and until the Senate votes to remove him or her at the end of an impeachment trial; in contrast, should Congress be called upon to decide the question of the president's ability or inability under Section 4, presidential authority remains in the hands of the vice president (as acting president) unless and until the question is resolved in the president's favor.

Article II, Section 1, Clause 6 of the Constitution reads:

In Case of the Removal of the President from Office, or of his Death, Resignation, or Inability to discharge the Powers and Duties of the said Office, the Same shall devolve on the Vice President ...

This provision is ambiguous as to whether, in the enumerated circumstances, the vice president becomes the president or merely assumes the "powers and duties" of the presidency. It also fails to define what constitutes inability or how questions concerning inability are to be resolved. The Twenty-fifth Amendment addresses these deficiencies. The ambiguities in Article II, Section 1, Clause 6 of the Constitution regarding death, resignation, removal, or disability of the president created difficulties several times:

• In 1841, William Henry Harrison died in office. It had previously been suggested that the vice president would become acting president upon the president's death, but Vice President John Tyler asserted that he had succeeded to the presidency, instead of merely assuming its powers and duties; he also declined to acknowledge documents referring to him as "acting president". Although Tyler felt his vice presidential oath obviated any need for the presidential oath, he was persuaded that being formally sworn in would resolve any doubts. Accordingly, he took the oath and title of "President", without any qualifiers, moved into the White House, and assumed full presidential powers. Though Tyler was sometimes derided as "His Accidency", both houses of Congress adopted a resolution confirming that he was president. The "Tyler precedent" of succession was thus established, and subsequently Vice Presidents Millard Fillmore (1850), Andrew Johnson (1865), Chester A. Arthur (1881), Theodore Roosevelt (1901), Calvin Coolidge (1923), Harry S. Truman (1945), and Lyndon B. Johnson (1963) were all deemed to have become president on the death of incumbent presidents.
• In 1893, Grover Cleveland secretly had cancer surgery, after which he was incapacitated for a time and kept from public view.
• Following Woodrow Wilson's stroke in 1919, no one officially assumed his powers and duties, in part because his wife, Edith Wilson, and the White House physician, Cary T. Grayson, kept his condition secret. By the time Wilson's condition became public knowledge, only a few months remained in his term and Congressional leaders were disinclined to press the issue.
• Up to 1967, the office of vice president had become vacant 16 times when the vice president died, resigned, or succeeded to the presidency. The vacancy created when Andrew Johnson succeeded to the presidency upon Abraham Lincoln's assassination was one of several that encompassed nearly an entire four-year term. In 1868, Johnson was impeached by the House of Representatives and came one vote short of being removed from office by the Senate in his impeachment trial. Had Johnson been removed, President pro tempore Benjamin Wade would have become acting president in accordance with the Presidential Succession Act of 1792.
• After several periods of incapacity due to severe health problems, President Dwight D. Eisenhower attempted to clarify procedures through a signed agreement with Vice President Richard Nixon, drafted by Attorney General Herbert Brownell Jr., but this agreement had no legal authority. Eisenhower suffered a heart attack in September 1955 and intestinal problems requiring emergency surgery in July 1956. Each time, until Eisenhower was able to resume his duties, Nixon presided over Cabinet meetings and, along with Eisenhower aides, kept the executive branch functioning and assured the public the situation was under control. But Nixon refused to use the president's White House office or sit in the president's chair at Cabinet meetings.

The 1951 novel The Caine Mutiny and its 1954 film version influenced the amendment's drafters. John D. Feerick told The Washington Post in 2018 that the film was a "live depiction" of the type of crisis that could arise "if a president ever faced questions about physical or mental inabilities but disagreed completely with the judgment", a situation the Constitution did not address. Lawmakers and lawyers drafting the amendment wanted no such "Article 184 situation" in which the vice president or others could depose the president merely by saying that he was "disabled".

In 1963, Senator Kenneth Keating of New York proposed a Constitutional amendment that would have enabled Congress to enact legislation providing for how to determine when a president is unable to discharge the powers and duties of the presidency, rather than, as the Twenty-fifth Amendment does, having the Constitution so provide. This proposal was based upon a recommendation of the American Bar Association in 1960.

The text of the proposal read:

In case of the removal of the President from office or of his death or resignation, the said office shall devolve on the Vice President. In case of the inability of the President to discharge the powers and duties of the said office, the said powers and duties shall devolve on the Vice President, until the inability be removed. The Congress may by law provide for the case of removal, death, resignation or inability, both of the President and Vice President, declaring what officer shall then be President, or, in case of inability, act as President, and such officer shall be or act as President accordingly, until a President shall be elected or, in case of inability, until the inability shall be earlier removed. The commencement and termination of any inability shall be determined by such method as Congress shall by law provide.

Senators raised concerns that the Congress could either abuse such authority or neglect to enact any such legislation after the adoption of this proposal. Tennessee senator Estes Kefauver, the chairman of the Senate Judiciary Committee's Subcommittee on Constitutional Amendments, a longtime advocate for addressing the disability question, spearheaded the effort until he died in August 1963. Keating was defeated in the 1964 election, but Senator Roman Hruska of Nebraska took up Keating's cause as a new member of the Subcommittee on Constitutional Amendments.

By the 1960s, medical advances had made it increasingly plausible that an injured or ill president might live a long time while incapacitated. The assassination of John F. Kennedy in 1963 underscored the need for a clear procedure for determining presidential disability, particularly since the new president, Lyndon B. Johnson, had once suffered a heart attack and—with the office of vice president to remain vacant until the next term began on January 20, 1965—the next two people in the line of succession were the 71-year-old speaker of the House, John McCormack, and the 86-year-old Senate president pro tempore, Carl Hayden. Senator Birch Bayh succeeded Kefauver as chairman of the Subcommittee on Constitutional Amendments and set about advocating a detailed amendment dealing with presidential disability.