Some severe auto-immune diseases, including rheumatoid arthritis, require immunosuppression to save life or vital organ function. One major limiting factor in such immunosuppression is the unwanted and dangerous haematoablation occurring at the same time. It is now possible to give supralethal doses of haematoimmunoablative drugs, and to 'rescue' the patient with haematopoietic stem cell transplantation. There are case reports of patients with rheumatoid arthritis who have received bone marrow transplantation, now called haematopoietic stem cell transplantation (HSCT), for a conventional indication such as aplastic anaemia or malignancy, in whom a long lasting improvement of the arthritis was observed. However, not all cases have responded, and there are still many open questions concerning optimal treatment regimens. In addition, some animal model research has supported the concept of HSCT as a permanent treatment of auto-immune disease including arthritis. In the past three years, HSCT has been applied to treat auto-immune disease alone in around 180 patients, 20 of whom having had rheumatoid arthritis and 13 juvenile arthritis. Early results are encouraging, but many issues require further clarification through co-ordinated clinical trials. The evolution of this project, details of the early results, the remaining open questions and possible strategies to resolve these are the subject of this chapter.