Severe autoimmune diseases are not cured by current conventional treatments. Preclinical studies of treatments requiring stem cell transplantation have shown sustained remissions in some models of autoimmune diseases. Both autologous stem cell transplantation after high-dose immunoablative therapy and allogeneic stem cell transplantation have a profound effect on the recipient's immunological system. Pilot clinical studies of autologous stem cell transplantation are being conducted. Sustained remissions will require the induction of tolerance to autoantigens during recovery. In a group of patients highly selected to minimize transplant-related mortality, allogeneic stem cell transplantation should be tested to determine if elimination of the autoreactive immunological system will achieve sustained remissions. These are promising therapies which will require long-term follow-up of patients to evaluate efficacy.