Following promising results in animal studies showing that immunosuppression and consecutive allogeneic bone marrow transplantation has the potential to significantly reduce autoimmunity, emerging data is supporting a benefit in patients with multiple sclerosis (MS) and other autoimmune disorders not responding to approved therapies. Until today, results on over 400 cases have been reported by the European Blood and Marrow Transplantation Group (EBMT), many of them with a favorable outcome. However, results of randomized, controlled clinical trials are missing. Furthermore, with upcoming new treatment compounds that to some extent act via lymphoablative properties, it remains essential to better select those patients who might profit most from stem cell therapy based on a justifiable benefit-to-risk ratio.