Induction of tolerance is likely to be necessary for the achievement of successful xenotransplantation, because immune responses against xenogeneic tissues or organs are vigorous. Currently, protocols that allow prolongation of xenogeneic grafts in preclinical large animal models are not clinically applicable, because the immunosuppressive regimens induce significant morbidity and mortality. This review focuses on the progress that has been made in the strategies that aim to induce donor-specific xenogeneic tolerance, which are largely based on the transplantation of thymic tissue, the induction of molecular chimerism, and the induction of mixed hematopoietic cell chimerism. Curr Opin Organ Transplant 2003, 8:83-88. © 2003 Lippincott Williams & Wilkins.