Polyreactive (auto)antibodies are frequently found in healthy subjects and are bona fide considered to be nonpathogenic. However, autoreactive B cells and circulating (auto)antibodies have been associated with several neurological syndromes, including demyelinating disorders. Whether these antibodies can have a real impact on disease development is still a matter of debate. Here, we briefly summarize some of the most recently published data on both the deleterious and the protective effects of antibodies in autoimmune demyelinating disorders of the central nervous system.