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From its origination involving successful rat hind-limb allograft studies using cyclosporine, face and upper extremity composite tissue allotransplantation has since developed into an exciting and promising subset of reconstructive transplant surgery. Current surgical technique involving composite tissue allotransplantation has allowed optimal outcomes in patients with massive facial and/or upper extremity defects; however, with its coexisting immunologic barrier, obligatory lifelong immunosuppression commits each patient to a daily risk of transplant-related complications with many unanswered questions. Since 1998, nearly 50 hand transplantations in 40 patients have been performed around the world at various levels ranging from wrist level to shoulder level. However, the risk-to-benefit ratio remains controversial in bilateral versus unilateral transplantation and has yet to be determined. From recent experience, the two most important determinants of the success of each patient's upper extremity transplant are patient compliance and intense rehabilitation. A total of nine face transplants have been performed since 2005. Multiple aesthetic subunits (i.e., nose, lips, eyelids) with or without underlying craniofacial skeletal defects (i.e., maxilla, mandible) have been successfully restored, thereby providing restoration of vital facial functions (i.e., smiling) in an unprecedented manner. As of today, face transplantation carries an estimated 2-year mortality of 20 percent. Concomitant composite tissue allotransplantation, which involves a variable combination of allograft subtypes, has been performed in two of the nine face transplant patients. These have included simultaneous bilateral hand transplants and tongue with mandible. Future study is warranted to investigate the potential advantages and disadvantages of using this approach versus a staged approach for reconstruction.