Hand transplantation is a form of vascularized composite allotransplantation under clinical research, which presents a novel therapy to amputation. Preparation for hand transplantation requires a carefully selected candidate, an extensive preoperative workup, and organization of a large, multidisciplinary team and a robust research infrastructure, among others. Performing a hand transplant involves a complex coordination of the teams from organ procurement and recipient surgery. Postoperatively, hand transplant recipients must undergo extensive occupational therapy, monitoring, and immunosuppression for as long as they have the transplant. Allograft rejection is a common complication of hand transplantation. However, complications may also be secondary to immunosuppression, which represents an important consideration in the decision-making between risk versus benefit. Advances in vascular surgery, immunology, microsurgery, and hand surgery allowed for the first successful hand transplant in 1998, and now over 150 hand transplants have been performed worldwide with preliminary positive functional outcomes. Both positive and negative psychosocial outcomes have been recorded. As an experimental procedure, many parameters, including patient selection criteria, immunosuppression regimens, outcomes, and monitoring protocols, have yet to be standardized. Innovation, systematic study, and practice will move forward the field of hand transplantation. This chapter provides a comprehensive review of key preoperative, intraoperative, and postoperative considerations, complications, and outcomes, as well as areas of active research in vascularized composite allotransplantation.