The role of blood and blood products in the acquisition of cytomegalovirus (CMV) infections following transfusion is reviewed. Considerable circumstantial data strongly suggest that primary infection and reactivation or reinfection with CMV occur frequently after transfusion. The incidence of these infections appears related both to the number of donors and to the volume of blood received by a patient. CMV infection following transfusion is most likely secondary to reactivation of latent virus either in donor white blood cells or host tissues. Recent studies of neonatal CMV infections acquired following transfusion proved that blood donors with antibodies to CMV (seropositive) are the source of CMV infection for patients lacking antibodies to CMV (seronegative). These primary CMV infections can be prevented by using only blood products from seronegative donors. Most CMV infections acquired after transfusion are either asymptomatic or characterized by a self-limited infectious mononucleosis syndrome. There are, however, specific groups of patients for whom a primary CMV infection after transfusion may cause significant morbidity and/or mortality. The patients at risk are seronegative and include pregnant women, premature infants, recipients of organ transplants from seronegative donors, and limited groups of severely immunosuppressed oncology patients. Current data suggest that for these seronegative patients the use of blood products from seronegative donors is both appropriate and likely to prevent posttransfusion CMV infection.