Hand transplantation (HTx), a non-life saving reconstructive procedure, significantly improves the quality of life of upper limb amputees. However, HTx recipients need to take immunosuppressive drugs for the remainder of their lives and, despite dramatic improvements in the safety of modern immunosuppressive protocols, these patients continue to suffer from adverse effects, a fact which raises ethical doubts regarding the legitimacy of HTx given its non-life saving nature. Furthermore, the effectiveness of immunosuppressive treatment in preventing chronic rejection remains unclear. In order to circumvent these important impediments, the ultimate goal of composite tissue allografting (CTA) needs to be the induction of donor-specific tolerance. A possible way of attaining this objective may be chimerism, the coexistence in the host organism of 2 populations of cells of both donor and recipient origin. Clinical experiments of solid-organ transplant recipients and CTA research in animal models provide promising perspectives for establishing chimerism with the use of the facilitating cells and regulatory T-cells. This article reviews the available data on achieved chimerism in HTx and the relevant literature.