Some patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as tumor necrosis factor (TNF) inhibitors. In recent years, there has been growing interest in, and enhanced understanding of, the contribution of B cells to the immunopathogenesis of RA. Rituximab (RTX), a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of malignant lymphoma for almost 10 years. Efficacy of rituximab in RA has already been demonstrated in randomized control trials, and US Food and Drug Administration has approved the combination of RTX with methotrexate for use in patients with RA, who have had an inadequate response to one or more TNF antagonist therapies. The long-term efficacy, especially about joint damage, and long-term safety need to be further investigated.