Genes encoding anti-arthritic products can be transferred to intra-or extraarticular sites where their expression suppresses various aspects of the pathophysiology of arthritis. A variety of viral and non-viral vectors can be used for the in vivo or ex vivo delivery of such genes. Promising pre-clinical data have resulted from the application of these strategies in several animal models of disease. Genes showing efficacy in this way include these encoding interleukin (IL) -1Ra, IL-1sR, TNFsR, transforming growth factor beta (TGF-beta), IL-13, Fas L, IL- 10 and vIL-10. Two human arthritis gene therapy protocols are underway in the USA and Germany. Both studies involve the ex vivo transfer of an IL-1Ra cDNA to the metacarpophalangeal joints of patients with rheumatoid arthritis. Progress in developing gene treatments for arthritis has been rapid, and permits optimism about their ability eventually to improve the treatment of this group of diseases.