Selective B-cell depletion with anti-CD20 therapy is a promising novel treatment option for patients with refractory autoimmune disease. The anti-CD20 antibody, rituximab, is the first therapeutic monoclonal antibody to have been approved by the European Medical Agency (EMEA) and the US Food and Drug Administration (FDA) for the treatment of relapsed, low-grade, follicular non-Hodgkin's lymphoma. Rituximab is now being studied in a range of autoimmune diseases, most notably rheumatoid arthritis, but also chronic immune thrombocytopenic purpura and systemic lupus erythematosus. Current data obtained from studies of rituximab single-agent therapy for autoimmune disease show good tolerability and sustained improvement in disease symptoms, although the precise mechanisms of action in autoimmunity remain to be fully clarified. Future research is likely to be focused on the optimization of responses with rituximab-based therapy. However, early observations suggest that this approach is likely to yield significant clinical benefits in a wide range of organ-specific and systemic autoimmune diseases.