Although renal transplantation offers survival and quality of life advantages as a renal replacement therapy, a substantial proportion of transplant recipients develop worsening of preexisting medical diseases or new complications, including sequelae of rejection, new onset diabetes after transplantation (NODAT), hyperlipidemia, opportunistic infections, cancer, and other systemic diseases secondary to immunosuppression. Management of these problems can be a complex endeavor due to medication interactions that often affect immunosuppression levels. However, successful management of the chronic medical problems associated with renal transplantation can prolong the life span of the graft and the patient.