Licensed in 1987, zidovudine remains the only medication with proved efficacy for the treatment of disease caused by the human immunodeficiency virus (HIV). New information on the pharmacology (adults and children), effects of kidney and liver dysfunction on the disposition of the drug, and drug‐drug interactions have improved the way we use and monitor this agent. The serious toxicity associated with zidovudine has led researchers to develop safer dosage regimens. Also, recognition that zidovudine slows but does not halt progression of disease has increased the search for effective alternatives. The best‐studied agents are didanosine (2′, 3′‐dideoxyinosine, ddI), zalcitabine (2′,3′‐dideoxycytidine, ddC), and foscarnet.