Cytomegalovirus (CMV) remains the most common cause of congenitally-acquired infection in the United States and is a leading infectious cause of sensorineural hearing loss, cognitive delay, and permanent neurologic sequelae. Although most cases of congenital CMV infection are asymptomatic, significant morbidity and mortality exist for symptomatic infants and may also occur in asymptomatic ones. Diagnosis remains relatively straightforward, but treatment options are limited and associated with some toxicity. Efforts at prevention via vaccination, screening, and improved epidemiology deserve high priority to limit the impact of this common infection.