Reconstructive transplantation has emerged as clinical reality over the past decade. Long-term graft acceptance has been feasible in extremity and facial vascularized composite allotransplantation (VCA) under standard immunosuppression. Minimizing overall burden of lifelong immunosuppression is key to wider application of these non-life saving grafts. Allograft tolerance is the holy grail of many cell-based immunomodulatory strategies. Recent protocols using mesenchymal stem cells from bone marrow and adipose tissue offer promise and potential in VCA. This article provides an overview of the experimental basis, the scientific background and clinical applications of stem cell-based therapies in the field of reconstructive allotransplantation.