CD4⁺CD25⁺ Treg are pivotal for the maintenance of self‐tolerance and the adoptive transfer of Treg is envisaged for the treatment of autoimmune diseases and the induction of tolerance after allogeneic organ or stem cell transplantation. Owing to the paucity of natural Treg in peripheral blood, isolation of Treg for therapeutic purposes is cumbersome and not easily translatable into clinical trials. To circumvent such hurdles, many groups are exploring the de novo induction of Treg from conventional T cells for potential clinical applications. In this issue of the European Journal of Immunology, a paper examines the therapeutic efficacy of natural and induced Treg in a model of graft‐versus‐host disease and report that induced Treg rapidly lose their Treg features in an allogeneic environment and are unable to prevent disease. Thus, the stability of induced Treg is of major concern as discussed in this Commentary.