Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology. Recent advances have suggested that T cells play a critical role in the immunopathogenesis of RA. A variety of clinical trials using a number of monoclonal antibodies have confirmed the hypothesis that CD4+ T cells play a central role in propagating the disease. Moreover, these trials have suggested rational approaches for the treatment of RA in the future. Despite a comprehensive view of the immunopathogenic processes causing the manifestations of the disease, the underlying cause of RA remains unknown. Critical aspects of RA that might be important in the early diagnosis and prognosis of the disease remain to be delineated. These include the precise role of the association with gene products of the major histocompatibility complex and possibly the role of other genetic elements. In addition, there is no information concerning potential etiologic agents. Delineation of these issues should provide additional insight into RA and potential approaches to treatment and prevention.