Multiple sclerosis (MS) is a complex autoimmune disease of the CNS. At present, MS etiology remains unknown, but it is believed to be caused by environmental factors acting on a genetic predisposition. Several studies suggest that different microorganisms could play a role in triggering autoimmunity, through immunological cross-reactivity or molecular mimicry. An overview of the knowledge regarding the bacteria involved in MS is given, placing emphasis on the newest candidate proposed: Mycobacterium avium subsp. paratuberculosis. This review will focus on discussing several arguments that might support a causal role for Mycobacterium avium subsp. paratuberculosis as an etiologic agent in MS. Additionally, a possible mechanism is postulated attempting to explain how the bacteria could initiate autoimmunity.