Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution 
of B cells has been largely underestimated, and the disease was considered a 
T-cell-mediated disorder. However, newer evidence shows that B cells play a 
crucial role in the pathogenesis of MS via antigen-driven autoantibody responses 
and through the cross regulation of T-helper cells. As B cells express the 
surface molecule CD20 at all points of differentiation, it provides a specific 
target for monoclonal antibodies, and the development and clinical testing of 
anti-CD20 antibody treatments for MS have been successful. After some 
observations, some small clinical trials found positive effects for the first 
anti-CD20 therapeutic rituximab in MS; newer agents have been specifically 
evaluated, resulting in the development of ocrelizumab and ofatumumab. 
Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 
2017 by the Food and Drug Administration (FDA) and is also the first proven 
therapy to reduce disability progression in primary progressive MS. This is 
particularly significant considering that disease-modifying treatment options 
are few for both primary and secondary progressive MS. Ofatumumab, a fully human 
anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further 
investigated in phase 3 trials for relapsing forms of MS. In this review, we 
discuss in detail these two anti-CD20 agents and their advent for treatment of 
MS.