Before the advent of antiretroviral therapy (ART), CMV retinitis was a common, debilitating opportunistic infection in the HIV-infected population. ART has had such a favorable impact on the prevention and management of CMV retinitis that it can be considered in some ways to be CMV therapy. Currently available CMV directed antiviral therapies are quite successful at limiting vision loss, but in resource limited settings there is still significant morbidity associated with the disease. This review summarizes the pathology, diagnosis, clinical course and treatment of retinitis in the pre-ART era to provide context for the contemporary clinical scenario, and highlights current management strategies. Important questions concerning host correlates of susceptibility and ideal therapy in the context of drug resistance are also briefly reviewed.