Cytomegalovirus retinitis is the most common intraocular infection and the leading cause of blindness in patients with AIDS. Diagnosis is made on clinical grounds; a variety of other infectious and neoplastic retinitides should be considered in the differential diagnosis. Treatment with intravenous ganciclovir or foscarnet has been proven effective, but late complications of relapse, viral resistance, retinal detachment, and drug toxicity remain problematic. Approved and investigational drugs for the treatment of CMV retinitis are limited by their virostatic, rather than virocidal, properties. Because the efficacies of ganciclovir and foscarnet are similar, the choice of therapy should be based on systemic considerations such as drug toxicity and patient survival. The cost, toxicity, and limited efficacy of currently available therapy of CMV retinitis make the need for an effective prophylactic drug even more important.