Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years. B cells are now known to have multiple key roles in the pathogenesis of RA. Data is now available that indicates efficacy and safety of B-cell depletion with rituximab in the treatment of RA in a variety of patient groups. The clinical outcomes from these studies, together with its safety profile, have led to rituximab being licensed for the treatment of patients with RA who have failed to obtain benefit from anti-TNF-alpha agents.