Cytomegalovirus is ubiquitous. While most infections are asymptomatic, infants and children acquiring CMV may excrete the virus for years in spite of significant antibody responses. CMV may be transmitted vertically or horizontally. Transplacental passage of CMV leads to congenital infection of the neonate. The most severely affected infants are born to mothers who develop a primary infection early in pregnancy and have a suboptimal cell-mediated response. During the perinatal period, the virus may be acquired by the infant from infected breast milk, passage through an infected birth canal, or by blood transfusion. Full-term infants infected during the perinatal period, though usually asymptomatic, may present with rash, hepatomegaly, lymphadenopathy, and/or pneumonia. Perinatally acquired infections in sick preterm infants may cause significant morbidity and mortality. Although specific therapy for infected individuals is currently unavailable, the outlook for an effective vaccine is promising.