In the past 5 years approximately 500 patients worldwide suffering from severe autoimmune disease (AD) have received an autologous hematopoietic stem cell transplantation (HSCT) as treatment following high-dose chemotherapy. The EBMT and EULAR data base contains 370 registrations, the most frequently transplanted ADs being multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and idiopathic thrombocytopenic purpura (ITP). Around 70% responded initially well, with durable remission/stabilization seen more frequently in MS and SSc than in RA and SLE, the latter having around 2/3 relapses, the majority of which respond to simple agents. Overall 8% transplant-related mortality was seen with large inter AD differences (12.5% in SSc and only one patient in RA) probably reflecting the degree of vital organ involvement at the time of transplant. This phase I/II data has led to a running phase III randomized trial in SSc called the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial, and it will soon begin in MS (ASTIMS) and RA (ASTIRA). The concept of immunological "re-setting" has evolved, and needs to be confirmed by longer follow-up and the multicentre, international phase III randomized studies.