Research into the orthopaedic applications of gene therapy has resulted in progress toward managing chronic and acute genetic and nongenetic disorders. Gene therapy for arthritis, the original focus of research, has progressed to the initiation of several phase I clinical trials. Preliminary findings support the application of gene therapy in the treatment of additional chronic conditions, including osteoporosis and aseptic loosening, as well as musculoskeletal tumors. The most rapid progress is likely to be in tissue repair because it requires neither long-term transgene expression nor closely regulated levels of transgene expression. Moreover, healing probably can be achieved with existing technology. In preclinical studies, genetically modulated stimulation of bone healing has shown impressive results in repairing segmental defects in the long bones and cranium and in improving the success of spinal fusions. An increasing amount of evidence indicates that gene transfer can aid the repair of articular cartilage, menisci, intervertebral disks, ligaments, and tendons. These developments have the potential to transform many areas of musculoskeletal care, leading to treatments that are less invasive, more effective, and less expensive than existing modalities.