Human cytomegalovirus (HCMV) is the most common viral infection acquired by the developing human fetus and can result in damage to the developing central nervous system. Although vaccine development to modify this congenital infection is ongoing, the unique epidemiology of maternal HCMV infections appears discordant with strategies for vaccine development. Several characteristics of congenital HCMV infections suggest that the efficacy of vaccines designed to induce responses similar to those that follow natural infection will be limited.