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Kidney transplantation is the preferred choice of treatment of end-stage kidney disease (ESKD). Improvement in surgical techniques and immunotherapy has transformed the field of kidney transplantation. Patients undergoing a kidney transplant have a 95% and 90% graft survival rate at one and 5 years. Although advances in immunosuppressive agents have reduced the incidence of acute rejection, the outcome of kidney grafts is still limited by chronic rejection and complications of these medications. The goal of kidney transplantation is to use the combination of immunosuppressive agents that best optimizes allograft and patient survival while limiting drug toxicity and complications. In this review, the immunology of transplantation is described with a focus on current immunosuppressive agents used in kidney transplantation.