Human cytomegalovirus is a ubiquitous virus infecting all populations in the world. The structural complexity of the virus and its highly regulated replicative programme are mirrored by the diverse array of disease and syndromes attributed to this agent. A unifying mechanism which could account for the often severe organ dysfunction induced by HCMV remains elusive, but may include non-cytopathic alteration in cellular function as well as direct virus-induced cellular cytopathology. Although it is rarely the cause of an identifiable clinical syndrome in normal hosts, individuals with underlying developmental or acquired immnnodeficiencies are at risk for significant virus-induced disease. Severe and often organ and life-threatening disease have been documented in allograft recipients, patients with AIDS, and the developing fetus. The lack of cellular immune responses to HCMV has been associated with disease in allograft recipients and HIV-infected hosts, whereas the risk of fetal infection and disease has been correlated with the lack of pre-existing seroimmunity in women infected with this virus during pregnancy. The virus has adapted several modes of immune evasion which promote persistence and which probably add to its symbiotic relationship with the human host. Current antiviral therapies are relatively toxic but have been shown to be effective in several different groups of patients. Successful prophylaxis of virus-induced disease has been achieved by passive transfer of both cellular immunity and antiviral antibody, suggesting that protective immunity could be achieved by an appropriate vaccine.