Congenital CMV infection remains a major problem worldwide. Current therapeutic efforts with ganciclovir have been limited to babies with extensive disease. The potential utility for children with less severe disease remains to be determined. Hopefully, the availability of newer compounds with an improved safety profile that will soon enter clinical trials (GW1263) provides hope that treatment for children with congenital CMV can lead to enhanced efficacy. Similar to our understanding of the treatment of congenital Toxoplasma gondii infections, long-term therapy, even up to a year or longer may be required. Ideally, the best approach would be the development of an efficacious vaccine. Regardless, current clinical efforts define a new era for the treatment of congenital infections.