While generic substitution is not a new phenomenon, a number of factors have combined to markedly increase generic drug use. The most important factor is a 1984 law, the Drug Price Competition and Patent Term Restoration Act, which facilitates the entry into the marketplace of generic versions of brand name drugs. This law and Food and Drug Administration (FDA) policies are designed to approve for marketing generic drug products that are therapeutically equivalent to their brand name counterparts. With increased availability of generic drugs, physicians have expressed the need for more information about the FDA process for determining that generic versions of brand name drug products are both safe and effective and that generic drug products will produce the same therapeutic results as those achieved by the brand name products. This article describes FDA procedures for approving generic drug products and examines issues important to the prescribing physician, in particular, therapeutic equivalence. The article also describes the role of the states in generic substitution and the availability of information from the FDA on the therapeutic equivalence of drug products. (JAMA 1987;258:1200-1204)