Xenotransplantation using pig organs as source for transplant has the potential to overcome the severe shortage of human donor organs. Wide utilization of genetically-engineered pigs is enabling progress to be made in pig-to-nonhuman primate experimental models. Novel, non-nephrotoxic immunosuppressive regimens have largely overcome T cell rejection and a T cell-dependent elicited antibody response. Recent advances in understanding of the biology of xenograft rejection and zoonotic infections and the generation of alpha1,3-galactosyltransferase-gene knockout pigs have moved this approach closer to the clinical application. However, inter-species coagulation dysregulation is proving a major hurdle. Progress in islet xenotransplantation has been more encouraging controlling diabetes in nonhuman primates up to 6 months, though this has usually been achieved using immunosuppressive protocols that might not be clinically applicable. Further advances are required to overcome the remaining barriers.