Multiple sclerosis is an autoimmune disease that destroys myelin-forming oligodendrocytes of the CNS. While the damage can be partially controlled using anti-inflammatory cytokines and steroids, endogenous repair is insufficient to replace lost cells. Until now cell replenishment (transplant therapy) has been viewed as unlikely to succeed due to allograft rejection in this sensitized immune environment. However, advances in stem cell biology give new hope for deriving patient-specific, autologous oligodendrocytes which may tip the balance to favor repair. The challenge will be to engineer these cells to respond to cues that can target their migration into lesions for brain and spinal cord repair.