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Far from being a “benign” arthropathy, as it was initially characterized, psoriatic arthritis (PsA) affects approximately 0.2% of the US population and can be associated with considerable joint damage, symptomatology, and quality of life impairment. PsA shares many characteristics with rheumatoid arthritis (RA), and new, rationally designed drugs that are effective in RA also are proving active in PsA. Two such drugs, etanercept and infliximab, target tumor necrosis factor (TNF), a key component of the inflammatory response. This review discusses the rationale for and experience with the use of these agents in PsA. Etanercept is a dimeric fusion protein that binds specifically to TNF, blocking its interaction with cell surface TNF receptors. Infliximab is a chimeric (murine/human) monoclonal antibody that binds to TNF and inhibits its binding to its receptor. A randomized placebo-controlled trial of etanercept in PsA found statistically significant benefits for this agent in measures of arthritic activity and psoriatic severity. There have been anecdotal reports of the efficacy of infliximab in PsA, but results from controlled clinical trials of this agent in PsA have not been reported. TNF inhibitors represent new therapeutic options for patients with PsA. The potential advantages of treatment with etanercept and infliximab early in the disease course are discussed.