Every year, millions of people require upper extremity reconstructions due to reasons such as trauma, congenital upper extremity defects, and upper extremity infections requiring amputation. Traditional treatment options are prosthetic devices and autologous reconstruction. These options involve a prolonged and expensive rehabilitation process, multiple surgeries, and large donor site morbidity. Vascularized composite allotransplantation is a popular treatment option that involves microsurgery and immunological principles of medicine. It can improve the patient’s quality of life, causing the regaining of upper extremity’s lost function. On the other hand, it requires lifelong immunosuppression treatment in order to prevent transplant rejection. These medications bring their own risks with them such as metabolic adverse effects, opportunistic infections, and an increase in malignancy prevalence. After surgery, patients should be observed closely in order to assess side effects of immunosuppression drugs and inspect for the rejection signs. The risk-benefit ratio of administering immunosuppressive agents and evaluating allotransplantation indications must be carefully considered. With the development of surgical techniques, revisions of immunosuppressive drug protocols, and the emergence of new immunomodulatory drugs, the interest in this field is increasing. Also, with bioengineering technologies which accelerate postoperative rehabilitation process and strengthen the allotransplant function, it is hoped that vascularized composite allotransplantation as an reconstruction option will turn into a more profitable situation than in the past, considering risk-benefit ratio.