In the two years since arthritis gene therapy was last reviewed in this journal, there has been rapid progress on several fronts. Although vector development remains a slow process and long-term gene expression is not easily obtained, very encouraging preclinical data in animal models of arthritis are now emerging. Collectively, these demonstrate the principle that transfer of cytokine antagonist genes to joints has a marked anti-arthritic effect. Other options under active investigation are the transfer of cytotoxic genes to effect a surgical synovectomy, and the transfer of oligonucleotides that antagonise the actions of transcription factors. Two human clinical trials of gene therapy for rheumatoid arthritis have been initiated. There are now preliminary data suggesting that gene therapy may also be helpful in osteoarthritis, as well as in the repair of cartilage, meniscus, ligaments, tendons and bones.