Since the identification of human immunodeficiency virus (HIV) as the etiologic agent of AIDS, progress has been made in identifying steps in the life cycle of the virus and the interactions between the virus and the host cell that may serve as targets for antiviral agents. Such information provides the basis for a rational approach to the development of anti-HIV drugs and suggests that combinations of drugs acting at different sites in the HIV life cycle can be studied. In vitro synergy has been demonstrated for several such combinations. While many compounds have shown promise in vitro, only zidovudine (AZT), a 2',3'-dideoxynucleoside analogue, has demonstrated efficacy in a controlled clinical trial and has been licensed for the treatment of certain subsets of patients with HIV infection. However, other drugs are in phase I and II clinical trials in the United States as well as abroad. In the United States, a national program for the timely identification and preclinical and clinical study of agents with activity against HIV has been established and promises to serve as an effective mechanism for the development of effective chemotherapy against HIV.