The present success of organ transplantation is largely due to advances in immunosuppressive therapy. Progress has been made from a cytotoxic strategy associated with a high morbidity rate to a strategy that seeks to alter the activity of cells that regulate the immune response, in order to selectively dampen antidonor responses. This article presents a comprehensive review of the clinical matrix of immunosuppressive agents, which includes various combinations of pharmacologic agents tailored to minimize toxicity and to enhance efficacy.