For recipients of a solid organ transplant, cytomegalovirus infection causes many pathological conditions including direct and indirect effects, most notably owing to the potency of the immunosuppressive medications used. Effects attributed to cytomegalovirus infection include graft rejection, decreased graft and patient survival rates, predisposition to other opportunistic infections, virally mediated malignancies, and various injuries specific to the transplanted organs (eg, accelerated coronary atherosclerosis following heart transplant, bronchiolitis obliterans syndrome in lung transplants, and vanishing bile-duct syndrome in liver allografts). Other indirect effects include posttransplant lymphoproliferative disorders, posttransplant new onset diabetes, and recurrence of hepatitis C virus infection. Direct effects are related to viral burden, whereas indirect effects may be observed even in the presence of low levels of cytomegalovirus replication. Being a function of the interaction between the virus and the host's immune and inflammatory responses, the underlying indirect effects of viral infection are not completely understood. Whereas it has been shown that cytomegalovirus prophylaxis can decrease the direct and indirect effects of the virus, recent data indicate that pre-emptive therapy has no long-term impact upon the indirect effects. Prevention of cytomegalovirus-related indirect effects might be achieved only with prophylaxis.