Cytomegalovirus (CMV) is a prevalent viral pathogen. The majority of persons with acute CMV will experience an inapparent infection. Primary CMV infection will cause up to 7 percent of cases of mononucleosis syndrome and will manifest symptoms almost indistinguishable from those of Epstein-Barr virus-induced mononucleosis. CMV, or heterophil-negative mononucleosis, is best diagnosed using a positive IgM serology. Complications of acute CMV infection in immunocompetent persons are rare, except in newborns. The virus usually is spread through close personal contact; transmission risk can be reduced by following simple hygienic and handwashing techniques. Severe illness can occur after reactivation of the latent virus in immunosuppressed persons. The retina is the most common site of CMV-induced pathology in persons with human immunodeficiency virus infection. Advances in the treatment of human immunodeficiency virus infection with highly active antiretroviral therapy (HAART) have decreased the incidence of CMV retinitis but have resulted in a new set of ophthalmologic complications induced by restoration of immune competency and the pro-inflammatory response of the patient to CMV. If HAART restores the patient's CD4 cell count to above 100 to 150 per mm3 (100 to 150 x 10(6) per L), it may preclude lifelong treatment for CMV retinitis.