Complex injuries to the upper extremities result in structural, functional and aesthetic deficits. Hand transplantation is a vascularized composite tissue allotransplantation with complex technical and immunologic challenges. The knowledge of hand transplantation is still evolving even after many successful procedures. Long– term immunosuppression with associated costs and complications are the real challenges in Hand transplantation and needs careful attention and consideration. Components of transplant program consists of protocols for donation of upper extremity, receipt selection for transplantation, surgical techniques, and immunosuppression. Ethical issues and financial considerations must be addressed well in advance to avoid complications and they are crucial for the success of the procedure. Post–operative rehabilitation, nerve regeneration are the important criteria that decide the final functional outcomes.