The ADA is based on four core concepts: disability, otherwise qualified, reasonable accommodation, and direct threat. Disability is defined much more broadly than traditional medical usage. In the congressional findings supporting the ADA, it was estimated that approximately 43 million persons were disabled by the standards of the ADA. The ADA defines disability, with respect to an individual, as the following:

1. a physical or mental impairment that substantially limits one or more of the major life activities of such individual;

2. a record of such an impairment;

3. or being regarded as having such an impairment.

The definition of disability is at issue for all three of the areas addressed by the ADA: access to public services and facilities, access to private services and facilities, and employment. "Otherwise qualified" and "reasonable accomodation" are at issue when a disabled person seeks employment. For example, a disabled individual who knows no computer programming languages would not be otherwise qualified to be a computer programmer. Reasonable accomodation refers to the steps the employer must take to help a disabled individual do a job. These can range from just providing a stool for a cashier with arthritis to a full time helper for a blind attorney. Even if a disabled person is otherwise qualified for a job, with or without a reasonable accomodation, the ADA does not require that person to be given the job if doing so would pose a significant risk to others. For example, a truck driver with impaired vision or who was prone to blackouts would pose a significant risk to others. Risk to self, despite some contrary language in the EEOC regulations implementing the ADA, is not sufficient reason to deny a person the chance to do a job. This is a change from previous law which allowed employers to refuse to hire persons who were at high risk of injury in a given job. Unfortunately, all of these terms are ambiguous and have generated substantial litigation.

The ADA covers only long-term disabilities, not those from acute illnesses or injuries that affect the worker for less than six months. The ADA specifically exempts illegal drug use, drunkenness, sexual preference (homosexuality, bisexuality, and transvestism), and pregnancy from the definition of disability. Beyond these specific exemptions, it provides that the employee's physical or mental condition cannot be considered except as directly relevant to job performance. This follows the existing law that limits educational testing to qualifications that are directly related to job performance. Employers may not use a calculus test to screen applicants for janitorial jobs, and they may not use blood sugar testing to screen potential secretaries.