We reviewed the epidemiologic characteristics, diagnosis, clinical features, and management of cytomegalovirus (CMV) infection after renal transplantation. CMV, the major viral pathogen after renal transplantation, increases patient morbidity and mortality. The spectrum of CMV infection ranges from latent infection to asymptomatic viral shedding to life-threatening multisystem disease. The two major risk factors for the development of CMV infection in renal transplant recipients are (1) preexisting CMV antibody seropositivity of either the organ donor or the recipient and (2) host immunosuppression. Blood cultures (but not urine cultures) positive for CMV predict the progression of asymptomatic infection to CMV disease, characterized by fever, malaise, myalgia, leukopenia, abnormal transaminase levels, and often involvement of the lung and gut. New genomic methods of viral detection now offer diagnostic advantages, including methods of detecting only actively replicating CMV. No evidence shows that CMV directly causes allograft rejection or glomerulonephritis, but patients with tissue-invasive CMV disease have higher rates of allograft loss and mortality than do those without the disease. Therapy for established CMV disease includes decreasing the immunosuppressive therapy and administering the antiviral agent ganciclovir sodium. Proven prophylactic strategies include limitation of exposure to the virus from CMV seropositive blood or organ donors, administration of CMV-specific immune globulin, and use of high-dose acyclovir therapy. Preemptive therapy with ganciclovir is a promising alternative to prophylaxis for patients at highest risk for progression to symptomatic CMV disease, such as those with CMV viremia and seropositive recipients receiving antilymphocyte therapy.