Our understanding of the role of B cells as part of the immune system has been remarkably expanded in the past few years. Autoimmunity, the production of autoantibodies or the activation and expansion of autoimmune T cells, is relatively common, whereas the development of autoimmune diseases with destruction of tissue is much less frequent. In rheumatoid arthritis, the autoantigen(s) involved in tissue damage and their role in disease have not been fully elucidated. Recent data suggest that the impact of B cells in rheumatoid arthritis may be of significance; therefore, a depleting anti-B cell therapy appears to be another therapeutic strategy. This review will focus on recent findings of the role of B cells in rheumatoid arthritis and the implications to target B cells in this disease.