Cytomegalovirus (CMV) is a common opportunistic infection in individuals with AIDS. Moreover, CMV retinitis represents a significant portion of end-organ disease in patients with CMV and AIDS. Prior to the advent of highly active antiretroviral therapy (HAART), almost one-third of people with AIDS developed CMV retinitis during their lifetime. Although effective therapies for CMV infection had been developed, treatment was often life-long due to persistent immune deficiency. Despite chronic suppressive maintenance therapy, disease relapse was nearly universal, and development of drug resistance was not uncommon. Widespread use of HAART has reduced the incidence and complications of CMV retinitis. With sustained immune recovery, discontinuation of anti-CMV therapy has been possible in many patients. Still, immune recovery does not guarantee protection from recurrent disease. CMV retinitis and uveitis associated with immune recovery remain causes of vision loss in this population and demand vigilance on the part of physicians.