The determinants of cytomegalovirus (CMV) infection and disease can now be understood from studies of newborns, recipients of organ or bone marrow transplants, subjects infected with human immunodeficiency virus, and recipients of blood transfusions. CMV is transmitted to the neonate transplacentally, by passage through a contaminated birth canal, or by ingestion of infected breast milk; to the adult by heterosexual and homosexual sex with an infected partner; and to the transplant recipient by infected organs. A major unsolved problem in the study of CMV is the nature of viral latency. Knowledge regarding the requirements for activation of latent infection at the molecular, cellular, or host level is incomplete. Both viral and host factors may contribute to the successful transmission of CMV by latently infected cells in transplanted organs and transfused blood.