Despite the current limited understanding of the etiology of multiple sclerosis (MS), genetic susceptibility and environmental influences are known driving factors. MS is considered a T-cell-mediated disease given the prevalence of T cells in plaques. Plaque formation is characteristic of this disease attributable to immune mechanisms, triggered by an autoimmune attack aimed at antigens in the myelin sheath or oligodendrocyte proteins. The attack consists of the following: The role of the B cells is twofold: first, as autoreactive B cells they produce autoantibodies, secrete cytokines, clonally replicate memory B cells, and long-living plasma cells which serve to advance the diseased state by their constant production of autoantibodies. Second, as antigen-presenting cells they activate the autoreactive T cells. For this reason, the stipulation that T cell is the cornerstone of MS must be reevaluated. Various studies on pathogenesis of MS have indicated that B cells, as the humoral component of the adaptive immune system, are active participants in pathogenesis and lesion maintenance throughout the disease process. The active role of B cells and autoantibodies makes them an encouraging therapeutic target. Advances in the understanding of B-cell development and activity would allow for an enhanced strategy in the design of autoimmune treatment. For this reason, further investigation is necessary to determine whether depletion of B cells or antibodies may restore immune function.