The impact of prophylactic oral ganciclovir therapy on the incidence of cytomegalovirus (CMV) disease, patient and graft survival, and costs in patients receiving kidney and liver transplants is described. CMV disease is a common cause of morbidity and mortality in solid organ transplant recipients unless prophylactic drug therapy is used. Prophylactic oral ganciclovir therapy reduces the incidence of CMV disease in kidney and liver transplant recipients. It is more effective for recipients who are seronegative before the transplant and receive organs from seronegative (D-/R-) donors than in seronegative recipients of organs from seropositive (D+/R-) donors. CMV disease remains a problem in the latter. CMV disease increases the risk of graft failure, which decreases the likelihood of patient survival. The extent of matching of the DR subregion of the human leukocyte antigen complex in the donor and recipient may affect graft survival in patients with CMV disease. Graft failure is costly and should be considered in economic analyses of CMV prophylaxis regimens because of the potential impact of prophylaxis on CMV disease. The use of oral ganciclovir for CMV prophylaxis has reduced the incidence of CMV disease in kidney and liver transplant recipients.