Rituximab, a human-mouse chimeric CD20 monoclonal antibody that depletes CD20-positive B cells, has already demonstrated efficacy in hematologic and rheumatologic diseases. Treatment with rituximab results in depletion of CD20-positive cells via multiple mechanisms, including complement-mediated or antibody-dependent cytotoxicity and apoptosis. Recent histopathologic and immunologic studies reveal an influence of B cells on the development and perpetuation of many chronic inflammatory diseases of the nervous system. Promising results with rituximab were already reported in the therapy of myasthenia gravis, immunoneuropathies, neuromyelitis optica, and multiple sclerosis, in which first controlled studies have been recently published. In this review we summarize available data from these reports and also discuss possible underlying molecular mechanisms.