Human cytomegalovirus (CMV) is a ubiquitous [beta] human herpes virus that establishes lifelong infection. Primary CMV infection in immunocompetent individuals is generally asymptomatic, but in congenitally infected children and in transplant patients CMV causes significant morbidity and mortality. Based on the life-time cost to the health care system and its impact on human suffering, development of a vaccine to prevent congenital human cytomegalovirus (CMV) infection has been assigned the highest priority by the Institute of Medicine of the National Academy of Sciences (US) and US National Vaccine Program Office. Therefore there is an emerging need for the development of an effective CMV vaccine. The main objective of vaccine development against CMV is to reduce the risk of CMV associated injury to the developing fetus and in immunocompromised individuals such as recipients of solid organ and hematopoietic stem cell transplants. In immunocompetent individuals CMV infection is maintained under strict control by the immune system by a combination of humoral and cellular immune responses. Thus, an effective CMV vaccine should be designed to induce virus-specific antibody, and CD4+ and CD8+ T cell responses. In spite of extensive efforts over the last 30 years, a clinically licensed vaccine formulation with convincing clinical efficacy remains elusive.