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Objective To perform a systematic review on the recent advances in immunosuppression for kidney transplantation and how these recent strategies over the past decades have led to significant improvements in the field of renal transplantation. Data sources MEDLINE, EMBASE, and Cochrane databases were searched. The search was performed on 1 November 2013 and included articles published ahead of print, with no language restrictions. Study selection The initial search presented 500 articles, of which 20 fulfilled the inclusion criteria. The articles studied whether transplantation is the ideal treatment for kidney failure, presenting details on graft immunology and the mechanism of action of immunosuppressants, with a focus on novel mechanisms. Data synthesis Because of heterogeneity in the postoperative follow-up periods and outcome measures reported, it was not possible to pool the data and carry out a meta-analysis. Comparisons were performed by a structured review. Conclusion Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been achieved at many renal transplant centers using currently available immunosuppressives, consisting of an induction agent, a calcineurin inhibitor, and an antiproliferative agent with or without a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while resulting in enhanced allograft outcomes. The aim of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.