Regeneration is a unique adaptation of skeletal muscle that occurs in response to injury. Following direct trauma or disease, regeneration results in restoration, to some degree, of the original structure and function of the muscle. Our purpose is to summarize the main features of the regeneration of skeletal muscle fibers and entire muscles with an emphasis on aspects of regeneration that may be important to the understanding and treatment of sports injuries. The regeneration of skeletal muscle is compared structurally and functionally with its embryonic development. The free muscle graft is used as a model to illustrate the integration of regenerating muscle with the rest of the body. Finally, the breakdown and regeneration of skeletal muscle fibers are discussed in relation to local anesthetics, sports injuries, and disease.