Despite remarkable improvement in short-term survival following organ transplantation, long-term results have been less satisfactory, mainly due to chronic rejection or toxicities induced by immunosuppressive drugs. Therefore, induction of specific immunologic tolerance remains an important goal in organ transplantation. Although numerous regimens for the induction of allograft tolerance have been developed in rodents, their application to large animal models has been limited. The mechanisms of action of the approaches that have been successfully applied in monkey models can be divided into three major categories: 1) deletion, 2) co-stimulatory blockade and 3) regulation. Long-term allograft survival has now been achieved in several nonhuman primate models; however, late-onset chronic rejection as well as the toxicity of some of these regimens remain as significant limitations that hamper clinical application.