Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T cells. Increasing evidence, however, suggests the fundamental role of B cells in the pathogenesis and development of the disease. Recently, anti-CD20 B cell-based therapies have demonstrated impressive and somewhat surprising results in MS, showing profound anti-inflammatory effects with a favorable risk-benefit ratio. Moreover, for the first time in the MS therapeutic scenario, the anti-CD20 monoclonal antibody ocrelizumab has been granted for the treatment of the primary progressive form of the disease. In this review, we provide a brief overview about anti-CD20 B cell-based therapies in MS, in the perspective of their influence on the future management of the disease, and of their possible positioning in a new wider therapeutic scenario.