Congenital and perinatal infection with human cytomegalovirus (CMV) are commonly encountered in newborns. In recent years there has been increased awareness of the disabilities that result from congenital CMV infection, which in turn has prompted interest in examining the potential efficacy of antiviral agents to prevent or ameliorate neurodevelopmental injury. Currently, there are three licensed systemic antivirals for the treatment of CMV: ganciclovir (Cytovene, Roche] and its prodrug valganciclovir [Valcyte, Roche); foscarnet (Foscavir, AstraZeneca); and cidofovir (Vistide, Pharmacia). A CMV-specific immunoglobulin is also available. Experience with these agents in the setting of congenital and perinatal CMV infection is very limited, but there are encouraging data from a controlled clinical trial indicating that ganciclovir therapy may be of value in limiting one form of neurodevelopmental injury caused by congenital infection, that of sensorineural hearing loss. Licensed antivirals for the treatment of CMV all share the common mechanism of targeting the viral DNA polymerase, but novel therapies that employ alternative modes of action are in development. Ultimately, the problem of perinatal CMV infection may be best controlled by the development of CMV vaccines, which could be administered to young women of childbearing age to help control this important public health problem.