Since the introduction of organ transplantation into medical practice, progress and optimism have been abundant. Improvements in immunosuppressive drugs and ancillary care have led to outstanding short-term (1--3-year) patient and graft survival rates. This success is mitigated by several problems, including poor long-term (>5-year) graft survival rates, the need for continual immunosuppressive medication and the discrepancy between the demand for organs and the supply. Developing methods to induce transplant tolerance, as a means to improve graft outcomes and eliminate the requirement for immunosuppression, and expanding the pool of organs for transplantation are the major challenges of the field.