Recent research has shown that the humoral response plays an important role in the pathogenesis of rheumatoid arthritis. B-cells produce rheumatoid factors and antibodies directed against cyclic citrullinated peptides (anti-CCP antibodies) and are able to present auto-antigens to T-cells. Furthermore, B-cells can produce cytokines and stimulate T-cells. B-cell depletion with rituximab, a monoclonal antibody directed against CD20, has a surprisingly strong and long-lasting therapeutic effect. After administration a sharp decrease of specific auto-antibody titres has been observed. Future developments in B-cell targeted therapy are expected to lead to further improvements in the treatment of rheumatoid arthritis and other autoimmune diseases.