Nonhuman primates (NHP), primarily rhesus macaques (Macaca mulatta) and cynomolgus macaques (M. fascicularis), serve as important preclinical models for solid organ and hematopoietic stem cell transplantation by providing an essential link in the translation of mechanistic approaches developed in mice to successful clinical therapeutic strategies. Although the central role of the major histocompatibility complex (MHC) in transplant biology has long been recognized, our knowledge of this system in NHP remains rudimentary compared to that of mice and humans. In this work, we review our current understanding of the MHC in macaques and the limitations it places on preclinical transplantation studies. We then discuss recent work from our laboratory that has identified cynomolgus macaques from the Indian Ocean island of Mauritius as an MHC-defined NHP population with exceptional potential for preclinical transplantation studies.