Because of the limitations of current therapies for rheumatoid arthritis (RA), novel approaches need to be developed for the treatment of this disease. Although certain antiinflammatory proteins such as soluble tumor necrosis factor-alpha receptor or interleukin-1 receptor antagonist protein are able to reduce certain pathologies associated with RA, there have been difficulties with targeting the proteins to sites of disease such as the joints. One novel approach for targeting proteins to sites of disease is to deliver the gene(s) encoding the therapeutic agent to specific cell types such as synovial cells or T-cells. Significant progress has been made towards developing gene therapy strategies for treating RA and the first clinical trial for the treatment of RA by gene therapy has been initiated recently. This review will summarize the approaches and progress made towards developing gene transfer methods for treating RA.