Hematopoietic stem cell (HSC) can be either allogeneic (from another person) or autologous (from the recipient). Autologous hematopoietic stem cell transplantation (HSCT) was first suggested by Burt as a form of intense immunesuppressive therapy. HSCT was proposed as a treatment for multiple sclerosis (MS) based on favorable results in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The toxicity and efficacy of an autologous HSCT is entirely a consequence of the conditioning regimen. Initial HSCT protocols employed aggressive malignancy-specific myeloablative regimens in patients with progressive MS. Unlike autologous HSCT, the immune compartment arising from allogeneic stem cells have a different and presumably more disease-resistant genetic predisposition towards disease recurrence. Both autologous and allogeneic HSCT require a chemotherapy conditioning regimen to suppress or ablate the immune system. HSCT is the only therapy to consistently demonstrate improvement in neurological disability.