Induction of transplantation tolerance remains a much sought-after but elusive goal with a potential promise of rendering patients free of long-term immunosuppressive drugs while maintaining good organ transplant function indefinitely. All currently studied strategies toward transplantation tolerance include using immunosuppressive agents for a limited time period to achieve tolerance. There are a growing number of agents that lend themselves to tolerance induction and these agents are considered herein. Such agents generally fall into the categories of lymphocyte depletion, costimulation blockade, and adjunctive agents such as rapamycin. Preliminary data using donor stem cells suggests that embryonic stem cells may have substantial advantages over conventional donor bone marrow for tolerance induction. These preliminary results are briefly reviewed as well. Tolerance has been achieved in a small number of organ transplant patients and such successes suggest that progress in the clinical arena is happening and is an obtainable result.