Human cytomegalovirus (HCMV) is the most common cause of intrauterine infection leading to birth defects in the United States and is among the most important opportunistic pathogens in immunosuppressed patients. Transmission may occur by direct contact with infected body secretions or by exposure to latent virus in blood products or organs from seropositive donors. In contrast, the developing fetus, organ and bone-marrow transplant patients, and patients with the acquired immunodeficiency syndrome frequently develop progressive, disseminated HCMV infections leading to multi-organ system damage and, frequently, death. The cytomegaloviruses are species-specific betaherpesviruses comprised of a double-stranded DNA genome enclosed by an icosahedral nucleocapsid, tegument, and envelope containing a large number of viral proteins and glycoproteins. Life-threatening HCMV infections resulting from primary exposure or reactivation of endogenous, latent virus are a frequent complication in patients with severe T-cell depletion and impairment of cell-mediated immunity.