Tumor necrosis factor antagonists such as infliximab and etanercept represent a new and powerful approach to managing RA. In studies published to date, TNF antagonists appear to be safe and effective agents for short-term therapeutic use in RA. Defining when in the course of RA to use TNF antagonists and determining the effectiveness of combinations of these biologic agents with DMARDs or other cytokine antagonists are areas of current and future studies. Other cytokine antagonists that may be promising subjects for further study are IL-1 antagonists. Like TNF, IL-1 is a member of the inflammatory cascade, but may play a different role in the development of inflammatory arthritis. In animal models, inhibition of TNF suppressed the inflammatory response while IL-1 antagonism prevented joint destruction (2). These results imply that combination therapy providing inhibition of both IL-1 and TNF might be an effective treatment in humans with RA, but clinical trials in humans have not yet been performed. Studies are underway in people with early RA to determine if the new TNF inhibitors are more effective or safer than currently available therapies, such as methotrexate. Other agents that inhibit TNF activity are also being tested at this time in people with RA.