The recent expansion of molecular biology techniques has opened the gates for a rapid advancement in our knowledge of disease mechanisms. These techniques, in addition to advances in cell biology and polymer chemistry, are resulting in novel approaches to treating musculoskeletal disorders. Surgeons, who have traditionally used the tools of excision and reconstruction to treat patients, might now serve as surgical 'gardeners', who create microenvironments that are conducive for tissue regeneration. This review will update readers on the principles and current advances in muscle-based gene therapy and tissue engineering for the musculoskeletal system.