Twenty-five years ago, on July 26, 1990, President George H. W. Bush signed the Americans with Disabilities Act (ADA), a historic moment when the polity gave voice to the nation's highest ideals. The ADA enshrined in law a social promise of equality and inclusion into all facets of life, while offering an inspiring model that much of the world would come to embrace. As a civil rights law coming in the wake of racial and gender equality legislation, the ADA has had profound symbolic meaning and real-world effects. Its promise of full participation in life stood in marked contrast to the oftenimpenetrable social and physical barriers that individuals with disabilities faced regarding inclusion in the workplace and public spaces. In sponsoring the ADA, Senator Edward Kennedy described life for persons with disabilities as an "American apartheid." 1 The ADA embodies the highest values of the United States-a compassionate nation with the vision to unleash the vast potential of persons with disabilities and to inspire global social change.Why should a medical journal like JAMA highlight the 25th anniversary of the passage of the ADA? Physicians care for many patients who have disabilities that are either preexisting or directly caused by injuries or disease processes. The ADA, moreover, directly affects health professionals and institutions by requiring nondiscriminatory treatment and reasonable accommodations for disabled patients. At the same time, physicians may develop disabilities and the statute affords them the same protection in the workplace as other workers. Importantly, medicine's highest values are its compassion, a deep empathy for patients, and an abiding commitment to respect and protect human dignity. It is natural, then, that a leading medical journal like JAMA would champion a social project as important as the ADA. Accordingly, this theme issue of JAMA includes 3 Original Investigations 2-4 that report novel research findings directly relevant to the ADA. The issue also features 6 scholarly Viewpoints 5-10 that address multiple aspects of the ADA, ranging from landmark Supreme Court rulings, to aspects related to employment and genetics, to considerations for health professionals with disabilities.The marginalization of persons with disabilities is in one sense remarkable because so many individuals have been, or will become, disabled. At any given moment, one-fifth of all individuals in the United States live with 1 or more disability, and many, perhaps most, will experience some form of disability during the life course. Although disability can occur at all ages, it is 8 times more likely in old age; one-fourth of Americans in their mid to late 60s have a severe disability, such as Opinion EDITORIAL Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association.