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Vascularized composite allotransplantation has become established as a clinical specialty since the first successful hand transplant was performed in 1998. Data now available indicate that hand and face transplants offer patients good functional outcomes and significant improvements in quality of life. Despite the debilitating nature of the injuries treated by such transplants, the defects are generally not life threatening, making it difficult for physicians to recommend life-long immunosuppression that can itself have grave consequences. One potential solution to this dilemma is the induction of immunologic tolerance of the tissue transplants because tolerance would eliminate the need for such immunosuppression. Transplant tolerance may also prevent chronic rejection, a significant source of late graft loss after organ transplantation.Induction of mixed hematopoietic chimerism is a robust approach to establishing such transplant tolerance, which recently led to the first clinical application of a tolerance induction protocol for kidney transplantation. In this manuscript, we review the current status of VCA and of research directed toward bringing a tolerance approach to the VCA field. We also discuss the potential clinical significance of these studies and outline the remaining obstacles to introduction of a tolerance induction protocol to clinical practice in hand or face transplantation.