Life-threatening opportunistic cytomegalovirus infection is a complication of the acquired immunodeficiency syndrome (AIDS) that occurs in 7.4% or more of patients with AIDS. Cytomegalovirus retinitis, colitis, esophagitis, and gastritis are the commonest manifestations of severe cytomegalovirus end-organ disease. Extensive trials with intravenous ganciclovir, a nucleoside analogue with myelosuppressive toxicity, have shown that ganciclovir halts the progression of cytomegalovirus retinitis and gastrointestinal disease. Since relapse is common when therapy is discontinued, most patients with AIDS need life-long maintenance therapy. The clinical response to ganciclovir therapy is usually accompanied by diminished shedding of the virus. Based on limited data, foscarnet, a pyrophosphate analogue, also appears to have some efficacy in treating cytomegalovirus infection. Unlike ganciclovir, foscarnet does not cause myelosuppression. An important direction for future clinical research is the development of more effective and less toxic therapy, as well as orally bioavailable drugs for maintenance therapy.