The pathogenesis of rheumatoid arthritis (RA) is a consequence of the activation of T cells by as yet unknown antigens and the co-stimulatory molecules CD4 and CD28. A number of potential antigens have been proposed for this process, including type II collagen, heat shock proteins and the glycoprotein gp39. Following activation, T cells initiate the inflammatory cascade through secretion of either interleukin 2 (IL-2) or interferon gamma, or through direct cellular interaction with macrophages and synoviocytes. Targeted therapies in RA are predominantly directed against the T cell. Results of several trials of anti-CD4 antibodies are being evaluated, including those of an anti-IL-6 receptor antibody, which showed short-term effectiveness but some toxicity, and an anti-intercellular adhesion molecule 1 antibody that caused dramatic reduction in rheumatoid factor titres. Non-antibody therapies of RA being studied include nasal administration of gp39 and oral administration of type II articular collagen, but the results of these studies have been equivocal.