Several therapeutic agents currently are used to treat rheumatoid arthritis (RA). However, there is no compelling evidence that any of these agents substantially alters the long-term destructive course of RA. Advances in biotechnology have led to a better understanding of mechanisms that underlie autoimmune diseases such as RA. Although the etiology of RA remains unknown, there now is considerable insight regarding the immune and inflammatory pathways that ultimately lead to cartilage and bone destruction. Therapies with monoclonal antibodies directed against cell surface constituents, fusion toxins against cell activation markers, and cytokine inhibitors all have been shown to be safe and possibly efficacious in early open trials in RA. They now are being more rigorously tested in double-blind, placebo-controlled trials. Early experience with these biologic agents in humans, as well as data obtained from the use of these agents in animal models of autoimmune disease, are reviewed. In addition, experimental studies with "blocking peptides" and immunization with autoreactive T cell receptor peptides will be reviewed, and implications for therapy in RA will be discussed.