Multiple sclerosis has traditionally been considered a T-cell mediated disease. Immunomodulatory therapy based on this theory reduces relapse rate but cannot completely prevent relapses or progression of disability and has generally negligible effect in the primary progressive form of the disease. B cells are crucial components of the pathogenesis of various autoimmune neurological disorders and play an important role in regulation of T cell activation, cytokine secretion and formation of ectopic germinal centres in the central nervous system. B cell follicle-like structures in the cerebral meninges represent an important site of B cell activation and expansion in chronic disease. After crossing the blood-brain barrier, memory B cells are susceptible to stimulation by antigens, clonal expansion, and differentiation in plasma cells that secrete antibodies. Besides being the target of the immunopathological process, central nervous system in patients with inflammatory disease provides a unique environment that supports the long-term survival of B-lineage cells, notably long-lived plasma cells, and local antibody production. Concept of B cell depletion by monoclonal antibodies that recognize specific target, CD20 antigen, represents potent therapeutic solution, with a strong influence on disease progression and proven efficacy in progressive form of multiple sclerosis, currently treated unsatisfactorily. Clinical trials have undoubtedly showed that anti-CD20 monoclonal antibodies elicit prompt and sustained suppression of inflammatory disease activity even after B cell reconstitution. The clinical impact was reflected in a substantial reduction in number and formation of new CNS lesion, and associated clinical relapses; also, a reduction of disability progression is reported. Transition to progressive phase of the disease can be reaped by an early therapy initiation. Additionally, promising effect on primary progressive multiple sclerosis was noted in terms of significant and sustained reduction of disability progression. Although the short-term safety profile appears favourable, long-term assessment of the safety profile of anti-CD20 monoclonal antibodies treatment is required in order to determine the risk of uncommon adverse effects, including PML or malignancies.