New insights into the pathogenesis of rheumatoid arthritis (RA) and consequently new targets of therapy are covered in a broad overview fashion. Short-term significant beneficial effect on RA disease activity has been established in a small but rapidly growing number of double-blind placebo-controlled trials now including recombinant human IL-1 receptor antagonist, chimeric (mouse/human) monoclonal antibodies (mAb) against TNF alpha (cA2), humanised (human/mouse) anti-TNF alpha mAb (CDP571) and recombinant human TNF-receptor-Fc fusion protein (TNFR:Fc). Placebo-controlled trials of anti-T cells agents such as chimeric anti-CD4 mAb (cM-T412) and anti-CD5 immunoconjugate, did not demonstrate clinical benefit. A placebo-controlled study of the anti-T cell derived cytokine IL-2 (DAB486IL-2) showed only modes clinical improvement. Other anti-T cell approaches such as autologous T cell vaccination and induction of tolerance by oral type II collagen have been unsuccessful. The one controlled trial with an anti-inflammatory cytokine, recombinant human IFN-gamma, showed modest clinical benefits. Controlled trials with IL-4 and IL-10 and with anti-adhesion molecules are awaited.