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Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by inflammation involving large and small joints. Systemic manifestations as well as involvement of paraoral tissues contribute to morbidity. Tumor necrosis factor (TNF) plays a central role in RA by amplifying inflammation in multiple pathways that lead to joint destruction. Tumor necrosis factor inhibitors were first licensed for clinical use in 1998; 3 have been approved for the treatment of RA: Iinfliximab, etanercept, and adalimumab. The purpose of this paper is to review the pathogenesis of RA, the state of the art of therapy, and the most current information on the safety and efficacy of TNF inhibitors for treatment of RA.