The congenital CMV infection is the most common intrauterine transmitted viral infection. Since the first description in 1904 a lot of knowledge on epidemiology has been gained. Socio-economic maternal factors play a major role, and seem to be one of the major reasons for the differences of prevalence of congenital CMV infection between Europe and North America. Concerning the interaction of CMV and placental cells, reactions of the host immune system have a dual effect - protection against the virus on the one hand, and supporting of virus production and release of CMV on the other hand. In the last years new strategies for prevention and therapy of congenital CMV infection have been investigated. Passive immunization for prevention of transmission of the virus seems to be promising, but also therapy with ganciclovir of congenital infected newborns showed good results. Taking the side effects of antiviral therapy into consideration, active and passive immunization may ultimately be the best control strategy for this important public health problem.