Congenital cytomegalovirus (CMV) infections are underrecognized as a cause of serious morbidity in newborn infants. The era of therapeutic nihilism regarding these infections has come to an end, however, as useful therapies are now available that may modify the outcome. The infected fetus can be treated in utero, or the newborn infant can be treated when CMV is recognized in the neonatal period. Expanded screening of newborns for congenital CMV infection will make it even more important for clinicians to be aware of current therapeutic options. The most effective option for the treatment of life-threatening or sight-threatening CMV disease at any age is the nucleoside analog ganciclovir. For the newborn with congenital CMV infection, the value of ganciclovir appears to relate to its ability to preserve hearing; other improvements in overall neurodevelopmental status are inferred but remain to be proven. In the pregnant woman with primary CMV infection, the use of CMV-specific immune globulin, though still investigational, is garnering attention and may prove to be a valuable therapy.