Tumor necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The agents, interfering specifically with the cytokine, have been produced to ameliorate disease activity of RA. There are only two reagents available in the Japanese market. Infliximab, a chimeric (mouse/human) IgG 1 monoclonal antibody to TNF-alpha, shows better efficacy in the combination with methotrexate (MTX) which reduces antichimeric molecule antibody responses in the RA therapy. Etanercept is a soluble form of human TNF type II receptor linked to an IgG 1-Fc moietry. Both TNF-alpha antagonists demonstrated excellent clinical efficacy and the addition of MTX at the early phase from the onset protected bone destruction. Infections are most frequent in their adverse effects.