The use of TNF alpha antagonists in RA has been extremely instructive. They have taught us that selective targeting of a pathogenic element can provide substantial clinical benefit. They have reinforced the concept of TNF alpha as a pivotal cytokine in the pathogenesis of RA. Pharmacodynamic studies of TNF alpha antagonists have further clarified the pathogenic processes involved in the disease. TNF alpha antagonists have set a new therapeutic standard for RA. Indeed, they are one of the most important advances in the history of the treatment of the disorder. If clinical efficacy is sustained and the safety profile remains benign over the long term, TNF alpha antagonists may replace MTX as the gold standard and become the agent of choice for combination therapy in RA. Further studies are needed to clarify their ultimate position in the therapeutic algorithm.