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Since 1998, when the first successful hand transplant was performed in France, at Lyon, an unpredicted development of reconstructive transplant surgery (transplant of VCA: vascularized composite allografts) occurred. Those procedures represents the only option for patients having extensive, complex tissue defects, involving multiple anatomical layers, impossible to approach using conventional reconstructive techniques. More than two hundred VCA procedures were reported worldwide, including: upper and lower limbs, face, larynx, trachea, abdominal wall, penis, uterus, knee allotransplant. Important aspects arise in the study of immunological mechanisms of acceptance and rejection of the allograft, the mode of action of immunosuppressive agents and protocols currently used in transplant programs for vascularized composite allografts. Immunosuppressive regimens that are used for solid organ transplantation (kidney, heart) are also effective for VCA transplants with good results regarding survival and functionality of the allografts. Current goal is the minimization of immunosuppression, composite tissue allotransplantation procedures being addressed for functional recovery (are not life-saving interventions like solid organ transplants). The ideal situation, which would allow a large scale utilization of VCA procedures, is the possibility of induction the donor-specific tolerance, allowing allograft acceptance without the need of immunosuppressive therapy. Currently this circumstance is difficult to achieve in clinical practice, resulting in large transplant centers ongoing research focusing on immunological difficult aspects. [ABSTRACT FROM AUTHOR]