The aims of this article are to discuss the potential role of B lymphocytes in the pathogenesis of multiple sclerosis (MS) and in the mechanisms of action of approved and emerging disease modifying therapies. Over the last few years, significant progress has been made in the introduction of novel pharmacologic treatments that reduce the frequency of clinical exacerbations and radiological lesion formation in relapsing remitting MS. The mechanisms of action of a number of these disease modifying therapies (DMT) implicate B cells in the pathogenesis, as well as in the regulation, of MS. Further research into B-cell subset trafficking patterns, functional activities and interactions with other immune cells in the context of neuroinflammation is likely to inform the development of future generations of DMT.