The advent of novel immunosuppressive agents with increased potency now offers multiple treatment options for transplant physicians. However, variable efficacy, drug-drug interactions, and adverse effects associated with long-term immunosuppression continue to complicate the clinical management of kidney transplant recipients. Currently, investigators are challenged to develop regimens that take into account not only efficacy, but also dosing, monitoring, safety, and patient quality of life. Recent research has focused on evaluating new combinations of approved agents that seek to improve outcomes by improving control of immunologic events with fewer complications. This article reviews current practice and recent studies to give all health care providers who manage kidney transplant recipients a better understanding of current regimens and general trends in immunosuppressive therapy.