Viral infections, particularly those involving HCMV, are an important complication of renal transplantation. Transplantation protocols and treatment regimens that increase HCMV infection and disease may promote the development of CRAD and impair long-term renal allograft survival. Investigators are beginning to illuminate the mechanisms by which HCMV infection may cause chronic rejection in general and transplant vascular sclerosis in particular. Migration and proliferation of SMCs within the intimal layer of blood vessels is an important component of transplant vascular sclerosis, and HCMV appears to facilitate both of these processes. Current management strategies for HCMV focus on prevention, either using a focal preemptive therapeutic approach or by administering antiviral therapies to all or at-risk patients.