Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovitis and bone destruction. Although anti-rheumatic drugs including methotrexate along with tumor necrosis factor (TNF) blocker markedly improved the disease activity, the treatment for the patients who failed to TNF blockers still has not been established. Recent clinical trials with CD20 antibody(rituximab and HuMax-CD20) provide sufficient evidence of excellent tolerability and high efficacy of therapy in refractory RA. A single course of rituximab, which is a genetically engineered chimeric murine variable regions/human IgG1 anti-CD20 monoclonal antibody, with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to one or more anti-TNF therapies.