The anti-CD20 antibody Rituximab was the first B-cell-specific therapy approved for the treatment of rheumatoid arthritis patients. The basis for its approval in 2006 was the REFLEX study, which examined the administration of 1000 mg Rituximab at 2-week intervals combined with Methotrexat compared with placebo in patients with poor response to TNF-inhibitors in terms of all relevant clinical parameters. Radiological data show that Rituximab is capable of effectively arresting joint destruction. The treatment was well tolerated. The most common side effect, seen in up to 35% of patients, was infusion reactions, particularly during initial Rituximab administration. This could be reduced by approximately 30% with the use of steroid premedication. The serious infection rate in this randomised trial was slightly increased compared with the placebo group, as would also be expected for other biologicals. Data on re-treatment is currently available for up to five treatments and show sustained and/or improved efficacy with continued good tolerance.