The therapeutic agents currently available to treat rheumatoid arthritis (RA)(disease-modifying antirheumatic drugs [DMARDs]) generally were not mitially developed for treating RA and, despite demonstration of superior efficacy of these agents compared with placebo, most DMARDs have not been shown to significantly reduce the destructive component of RA. However, with the use of methotrexate (MTX)(alone or in combination) earlier in the disease process, there is potential, with currently available DMARDs, to significantly alter the natural history of RA. Although the etiology of RA remains unknown, recent advances in molecular technology have made it possible to identify distinct cell subsets, cell surface markers, and cell products that contribute to the immune-mediated inflammatory responses associated with the disease. This enhanced understanding of the immunopathogenesis of RA, although still incomplete, provides opportunities to specifically target the immune response pathways using more specific therapies. This review will focus on the rationale for the iise of “biologic” agents as potential therapies for RA and will provide a summary of the results of clinical triials published to date.“Biologic” agents can be broadly defined, but generally include monoclonal antibodies (MAb) directed against selected cell surface markers (eg, CD4), or recombinant forms of natural inhibitory