Nearly 30 years have elapsed since Rowe and Weller and their colleagues discovered human cytomegalovirus (CMV). Because of its complex structure, long replicative cycle, low yield in vitro, and highly species-specific cell-substrate requirement, the cellular and molecular biologic analyses of human CMV have been slow, but recombinant DNA and monoclonal antibody technologies are bringing about rapid changes. Because of the long period of latency and wide range of disease presentations, epidemiologic and medical insights have also come slowly. However, the clinical events that occur during iatrogenic immunosuppression (transplantation and cancer therapy) and as a result of immunocompromise due to human immunodeficiency virus infection are currently promoting our understanding of the epidemiology of CMV disease and the definition of its clinical spectrum. Rapid diagnostic methods, antiviral drugs, and vaccines for CMV are becoming available. We may not yet understand completely the impact of this agent on the nonimmunosuppressed or aspects of its pathogenesis: e.g., the immune functions controlling recrudescence and the possibility of increased disease severity in those with no detectable immune defect. With the availability of new approaches, other issues should be clarified, such as the functions of host and virus involved in the mechanism of persistence.