Primary infection with cytomegalovirus (CMV) in seronegative patients is acquired most commonly from blood products or marrow taken from seropositive donors, whereas recurrent infection in seropositive patients appears to be derived predominantly from reactivation of latent endogenous virus. Not all infected patients develop symptomatic CMV disease; the factors that determine severity of infection and recovery are not yet fully defined. The epidemiology of CMV infection indicates that primary infection is preventable by use of seronegative blood products, including marrow. Such techniques should be implemented immediately. Leukocyte depletion of blood products is a potential alternative, but both efficacy and logistics of implementation require further study in patients who need large quantities of blood products. The efficacy of passive immunoprophylaxis with immunoglobulins remains uncertain, and this modality cannot be recommended until additional data are available. Among seropositive patients, antiviral agents may be used to suppress CMV infection until periods of improved immunocompetence. Although not effective for the treatment of established CMV infection, intravenous acyclovir significantly reduced the probability of CMV infection and disease and improved survival in a controlled trial. The newer antiviral agents ganciclovir and foscarnet should provide better protection, although the marrow toxicity of ganciclovir is problematic. Future directions will include attempts to restore specific immune responses with subunit or recombinant vaccines and adoptive immunotherapy with CMV-specific effector cells generated in vitro.