Current estimates suggest that at least 1 million persons in the United States are infected with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome. Knowledge of the life cycle of HIV has provided the fundamental information necessary to initiate programs that will identify drugs to treat the infection. Inhibition of reverse transcriptase represents the only strategy of proved clinical value. Three such drugs are available: zidovudine, didanosine, and zalcitabine. Zidovudine is the only proved agent for therapy of asymptomatic HIV infection; and for symptomatic disease, monotherapy with zidovudine must also be regarded as the first-line approach. For patients who are intolerant, are failing clinically, or have received prior long-term treatment with zidovudine, monotherapy with didanosine or zalcitabine, or a combination of zidovudine and zalcitabine are alternatives. Progress is being made in the treatment of HIV infection, but the considerable challenge to affect the inexorable progressive nature of HIV disease remains daunting.