The problems of immunosuppressive drug toxicity could be alleviated by induction of immune tolerance.Over the last 25 years, several strategies have been used successfully to induce transplantation tolerance. Each of these has been validated in at least one rodent model, with varying degrees of success upon extension to large animals, including nonhuman primates. Very small minorities of patients, who discontinue their immunosuppression, provide rare examples of clinical transplantation tolerance. To this purpose, mesenchymal stem cell (MSC) infusion could represent a novel tolerogenic cell therapy in kidney transplantation.