Environment and genetic are both relevant in determining development of Multiple Sclerosis. Many epidemiological observations converge on indicating EBV infection and Vitamin D levels as major players among the environmental factors. Bacteria and bacterial products are however potent triggers of immune responses, and recent work from several laboratories indicates that the microbiota plays a prominent role in "priming" or protecting individuals for development of experimental autoimmune diseases. Here we report our recent work dealing with the role of non-pathogenic mycobacteria and their innate receptors in relapsing-remitting experimental autoimmune encephalomyelitis in the SJL mouse and in mobilization of CNS-reactive T cells. We finally discuss how bacteria are likely involved in the pathogenesis of Multiple Sclerosis, expecially with regard to their role in driving the recurring acute episodes of disease.