Managing maintenance immunosuppressive regimens after kidney transplantation is often challenging and confusing, requiring careful attention to efficacy, dosing, adverse effects, and costs of multiple medications. Most protocols combine a primary immunosuppressant (cyclosporine or tacrolimus) with one or two adjunctive agents (azathioprine, mycophenolate mofetil, sirolimus, corticosteroids). Avoiding drug-drug interactions is a major part of effective immunosuppressant management, and special situations (eg, pregnancy, intravenous dosing, caring for minority patients) can prove especially daunting. This review summarizes available data regarding current practices in maintenance immunosuppression, emphasizing issues that arise in day-to-day management of renal transplant recipients.