Human cytomegalovirus (HCMV) is a herpesvirus that infects, and is carried by, 70%-100% of the world's population. During its evolution, the virus has adapted to survive in an immunocompetent host. For many years, HCMV was not considered to be a major human pathogen because it only caused rare cases of HCMV inclusion disease in neonates. However, HCMV is poorly adapted to survive in the immunosuppressed host and has emerged as an important human pathogen in AIDS patients, and in patients undergoing immunosuppressive therapy after organ or bone marrow transplantation. The virus is also the major infectious cause of birth defects. To coexist with its host, HCMV must avoid elimination by the immune system. Research over the past decade has revealed sophisticated mechanisms that enable the virus to remain invisible to cells of the immune system.