Cardiovascular disease is the leading cause of death following renal transplantation, and renal transplant patients have a greatly increased cardiac risk compared with the general population. Death with a functioning graft caused by cardiovascular disease also represents a substantial cause of graft loss. Decreased renal function in transplant recipients is a major contributor to increased cardiac risk, both as an independent risk factor and because of its negative effects on hypertension, anemia, left ventricular hypertrophy, and dyslipidemia. Graft loss and diabetes mellitus are also significant risk factors for cardiac death. Although critical for maintaining the transplanted organs, standard immunosuppressants have toxicities that exacerbate cardiac risk. Preservation of renal function, prevention of graft loss, and reductions in cardiovascular risk factors via improvements in both patient management and immunosuppressive therapies constitute critical strategies for optimizing patient and graft survival over the long term.