Rituximab is a monoclonal antibody against CD20 that was developed for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Recent controlled trials have shown that B cell-targeted therapy with rituximab is effective in RA (which suggest that B lymphocytes may be critical in its pathogenesis of RA) and early exposure data suggest that the tolerability and safety profile of rituximab may be even better in RA than in NHL patients. Rituximab is generally well tolerated, with a low incidence of serious adverse events, including serious infections. Available evidence suggests that its clinical benefits depend on effective B cell depletion, and the fact that its novel mode of action leads to the depletion of B cells makes it distinct from other biological therapies for RA that target T cells and their related cytokines. Although complete peripheral B cell depletion is regularly seen in RA and other autoimmune diseases, especially systemic lupus erythematosus (SLE), incomplete depletion has been reported in a subset of patients, even after full dosing with rituximab.