Gene therapy offers several novel advantages to the treatment of arthritis and other joint diseases. Therapeutic genes may be delivered locally to diseased joints or systemically to extra-articular locations using viral or non-viral vectors by ex vivo or in vivo strategies. Pre-clinical experiments with rabbits have demonstrated the utility of using a retrovirus to deliver the human interleukin-1 receptor antagonist to the synovial lining of joints. A human trial based on this principle has been approved by the Recombinant DNA Advisory Committee of NIH and should begin this year.