Recent advances in gene transfer technology permit the design of strategies to improve the outcome of orthopaedic tissue engineering by genetic means. Using ex vivo and in vivo strategies, genes have been transferred successfully to, and expressed within, numerous tissues of the musculoskeletal system, including articular cartilage, meniscus, intervertebral disc, bone, tendon, ligament, synovium, and muscle. With these technologies, various genes encoding modulatory species of ribonucleic acid or proteins such as growth factors, receptors, and transcription factors could be used in the context of genetically augmented tissue engineering. Proof of principle has been established in numerous animal models, and a human protocol for the transfer of genes to synovium already is underway. Progress so far permits cautious optimism of a successful outcome to these pursuits.