For the orthopedic sports medicine physician soft tissue injuries often present the greatest clinical problems. Not only do many of the most frequently injured tissues, such as the cruciate ligaments and articular cartilage, have very limited capabilities for spontaneous repair, but they also respond poorly to surgical or nonsurgical intervention. In this article we try to define the role of growth factors in these conditions and to outline concepts for future treatment based upon modulation of the native repair response. We suggest that gene transfer could improve the management of such injuries, particularly when used as vehicles for the targeted delivery of growth factors. The concept of gene therapy in orthopedic sports medicine can be extended to include disorders that present as laxity or mechanical weakness of ligaments. We speculate that subtle genetic differences between individuals may account for those who appear to be injury prone. In these cases it is likely that genes encoding the structural macromolecules of the matrix are defective. Local gene supplementation in such cases could be useful in the future.