Gene therapy is emerging as a promising approach in orthopedic sports medicine, aiming to enhance musculoskeletal tissue repair and regeneration. This chapter explores the principles, applications, and future directions of gene therapy in treating conditions such as articular cartilage defects, osteoarthritis, meniscus and ligament injuries, and muscle loss. Various gene transfer methods, including viral and nonviral vectors, are discussed, highlighting their advantages and limitations. Novel therapies such as scaffold-guided gene delivery and CRISPR-Cas9 gene editing are also discussed. While significant progress has been made in preclinical and early clinical studies, challenges remain in ensuring safety, efficacy, and regulatory approval. With advancements in gene editing technologies, biomaterials, and targeted delivery systems, gene therapy holds great potential to revolutionize treatment strategies in orthopedic sports medicine, offering improved outcomes for athletes and patients suffering from degenerative musculoskeletal disorders.