Multiple sclerosis (MS) is an autoimmune inflammatory disease of the CNS driven by the inflammatory activity of peripheral immune cells recruited to the CNS and by CNS-resident glial cells. MS pathogenesis has been linked to both genetic and environmental factors. In addition, the commensal flora have been shown to modulate immune processes relevant to MS pathogenesis. We discuss the effects of the gut microbiota on T cells and glial cells, and their relevance for the control of inflammation and neurodegeneration in MS. A better understanding of the gut-CNS axis will shed new light on the mechanisms of disease pathogenesis, and may help to guide the development of efficacious therapies for MS.