Osteoarthritis (OA) is common, debilitating, expensive, incurable and very difficult to treat. Gene transfer to the synovial linings of affected joints is a promising strategy for achieving sustained, therapeutic, intraarticular concentrations of anti-arthritic gene products. This is not reasonably possible with existing, alternative technologies. The present review summarizes progress in achieving direct, in vivo intraarticular gene delivery and expression. Numerous non-viral vectors have been evaluated for their ability to transfect the synovia of experimental animals following intraarticular injection. None have given more than low levels of temporary transgene expression and many are inflammatory. Several viral vectors, however, are very effective in this regard and successfully treat experimental models of OA. Adeno-associated virus has been used in a phase I study for the gene therapy of rheumatoid arthritis. Its use in a clinical trial for treating OA is pending.