Intrauterine infection with cytomegalovirus (CMV), a betaherpesvirus, remains the most frequent congenital virus infection in many regions of the world. Although most CMV-infected newborns lack signs of CMV infection, approximately 10% have signs that can consist of low birth weight, jaundice, hepatosplenomegaly, skin rash, microcephaly, and chorioretinitis. Neonates with signs of CMV infection at birth have high rates of audiologic and neurodevelopmental sequelae. Although postnatal therapy with ganciclovir transiently reduces virus shedding and may lessen the audiologic consequences of CMV in some infected infants, additional strategies are needed to prevent congenital CMV disease and to improve the neurodevelopmental prognosis of infants infected with CMV in utero. Some cases of intrauterine infections can be prevented in susceptible women by avoiding contact with the urine or saliva of young children who may be shedding CMV. Vaccines against CMV remain in the experimental stages of development. Termination of pregnancy can be offered to women whose infants have evidence of intrauterine CMV infection and sonographic signs of central nervous system damage. Infants who survive symptomatic intrauterine infections have high rates of neurodevelopmental sequelae and require comprehensive evaluation and therapy through center and home-based early intervention programs.