The current failure of potent immunosuppressive agents to control progressive disease in multiple sclerosis has moved a focus from immunotherapy towards the need for neuroprotection. There is increasing evidence for cannabinoid-mediated control of symptoms, which is being more supported by the underlying biology. However there is accumulating evidence in vitro and in vivo to support the hypothesis that the cannabinoid system can limit the neurodegenerative possesses that drive progressive disease, and may provide a new avenue for disease control.