Rituximab as a monoclonal antibody against CD20 was approved for treatment of patients with rheumatoid arthritis (RA) with inadequate response to or contraindication for the use of a TNF blocker. This article focuses on current results from clinical trials at different developmental stages as well as from registry data in anti-TNF non-responders regarding the documented efficacy with respect to RA activity, radiological progression and improvement of functional indices. The available safety data for rituximab for this particular indication showed that the overall risk of infection, including severe manifestations, is not further increased. The occurrence of progressive multifocal leukoencephalopathy (PML) after rituximab requires further observation; the risk has currently been estimated at about 1:15.000-20.000 of RA patients treated. Of relevance, decreased IgG levels prior to treatment have been reported to be associated with a substantially increased risk for infections, and therefore, in such cases other treatment options should be considered.