The authors describe the most critical aspects of transplantation of the hand. Three successful cases are presented from the Italian Hand Transplantation National Program. The key issues of this new type of surgical reconstruction for major amputations are selection criteria of suitable candidates, technical aspects of surgery, postoperative regime and functional rehabilitation. Other important aspects are staff requisites and organisation of the clinical trial, ethical and legal implications, dealing with the media. The authors comment on the fact that we might be ready to accept that almost anything could come from a cadaver, even if it is not a life-saving organ, to reconstruct missing parts and restore anatomical integrity and, especially, function.