Mother-to-child transmission of cytomegalovirus (CMV) can lead to severe birth defects and neurologic impairment of infants. Congenital CMV is the most common congenital infection and the leading infectious cause of infant hearing loss and neurologic deficits, complicating up to 2% of all pregnancies globally. Although antiviral treatment of congenitally CMV-infected infants can ameliorate CMV-associated hearing loss and developmental delay, interventions that can effectively prevent congenital CMV infection and the associated neurologic impairments are still being evaluated. Moreover, an effective CMV vaccine to protect mothers against CMV acquisition during pregnancy is urgently needed to reduce the sizeable health and economic burden of this disease. Active and passive maternal and infant immunization strategies to prevent symptomatic perinatal CMV infection are a critical need in pediatric health.