While current immunosuppressive drug regimens have significantly increased the rate of successful transplantation outcomes, they convey potentially serious and overlapping adverse effects. Cyclosporine and tacrolimus are the cornerstones of current immunosuppression, achieving excellent one-year renal graft survival rates. Other promising new drugs include sirolimus, which has been demonstrated to reduce efficacy failure rates among renal transplant recipients, and everolimus, which is currently undergoing clinical trials. Agents targeting novel sites in the immune response or disrupting the ischemia-reperfusion cascades are currently under development. Among them, only FTY720 is undergoing large-scale human clinical trials. With its unique mechanism of action and synergistic interactions with cyclosporine and sirolimus, it may provide the foundation for a new era in immunosuppression.