OBJECTIVE To review published literature using rituximab for treatment of refractory rheumatoid arthritis (RA). METHODS An English-language literature search was conducted using MEDLINE (1966-May 2005) and EMBASE (1980-May 2005). References of identified articles were subsequently reviewed for additional data. RESULTS Evidence suggests that B lymphocyte depletion in patients suffering from refractory RA may be a key component in the interruption of the disease pathogenesis. Successful depletion of B lymphocytes with rituximab in patients with RA has been reported in case reports, open-label pilot studies, and a randomized, double-blind, placebo-controlled trial. CONCLUSIONS Based on the limited published data, rituximab, when used in combination with other agents (ie, cyclophosphamide or methotrexate), appears to be a reasonable treatment option for refractory RA. However, additional controlled trials need to be conducted to further define optimal dosing, response rates, comparative long-term efficacy, and RA treatment algorithm placement of rituximab in this patient population.