Current nonspecific immunosuppression for thoracic organ transplantation is limited by infection, end-organ toxicity, malignancy, and failure to completely control rejection. Donor-specific transplantation tolerance after bone marrow transplantation and the creation of mixed chimerism is a promising means for achieving drug-free allograft acceptance. This review explores bone marrow transplantation as a method for tolerance induction, the superior clinical characteristics of mixed chimerism, and recent developments that enhance marrow engraftment, minimize graft-versus host disease, and avoid lethal conditioning of the recipient. The importance of microchimerism in clinical transplantation and clinical trials aimed at augmentation of this phenomenon are reviewed.