B-cell–depleting monoclonal antibodies (mAbs) have emerged as an arguably mechanistically dominant drug class in the multiple sclerosis (MS) disease-modifying therapy (DMT) armamentarium in recent years. As a group, they represent a high-efficacy treatment option for relapsing MS and offer some degree of efficacy in progressive forms of MS. Ocrelizumab remains the only DMT approved for primary progressive MS. Current approved CD20–targeted mAbs for relapsing forms of MS include ocrelizumab, ofatumumab, and ublituximab.