There have been several recent advances in the use of immunosuppression after organ transplantation. The main goal is to induce transplantation tolerance without immunosuppressive drug toxicity. We reviewed both experimental and clinical organ transplantation studies such as costimulatory blockade agents, sphingosine 1-phosphate receptor analogs, lymphocyte depletion strategies, and chemokine blockade agents in the context of renal transplantation. The newer and safer immunosuppression protocols might provide significant benefit to organ transplant recipients as alternatives to conventional immunosuppressive therapy.