Ganciclovir has been shown to be effective against cytomegalovirus (CMV) in vitro, but its role in the treatment of congenital cytomegalovirus infection is unknown. We describe its use in the management of two cases of congenital CMV infections. The drug was well tolerated and virus shedding in the urine was eliminated, though hepatosplenomegaly and neurodevelopmental delay persisted in both cases.