Morphologic changes observed in osteoarthritis include cartilage erosion and a variable degree of synovial inflammation. Proinflammatory cytokines such as interleukin-1 beta, locally produced by the inflamed synovium, also likely contribute to these alterations. Despite an extensive armamentarium and numerous surgical options, osteoarthritis remains incurable, and an improved approach in the treatment of this disease is imperative. Drug delivery is a major weakness of existing antiarthritic therapies. Local delivery of antiinflammatory cytokines or the in vivo induction of their expression using gene transfer may provide a novel approach for the treatment of osteoarthritis. Evidence of the efficacy of gene therapy in osteoarthritis remains very scarce. To the authors' knowledge, there is no clinical research protocol en route for the treatment of osteoarthritis using gene therapy. The authors present the only two studies that have proved successful in treating animal models of osteoarthritis using gene therapy, and propose an overview of several strategies for the development of gene therapy in osteoarthritis treatment in the future.