This chapter reviews the mechanisms for both inflammatory and non-inflammatory mediated neural degeneration in multiple sclerosis (MS) and discusses potential therapeutic targets for neuroprotection. The classical pathological description of the MS lesion has focused on the perivenular inflammatory infiltrate characterized predominantly by lymphocytes and monocytes. Progressive axonal loss occurs in the central nervous system (CNS) of patients with MS, and the extent of this axonal loss correlates with the degree of permanent neurological deficit. Careful consideration to the pathophysiology of MS is necessary to identify candidate drugs for therapeutic trials. Stem cells may serve to enhance the function of host tissues, to provide missing chemicals or enzymes or to halt a degenerative or neoplastic process. As the currently available immunomodulatory treatments for MS have only a modest impact on progressive axonal loss and disability, there exists a pressing need to develop strategies to prevent this axonal loss.