Skeletal muscle injuries are extremely common, accounting for up to 35%-55% of all sports injuries and quite possibly affecting all musculoskeletal traumas. These injuries result in the formation of fibrosis, which may lead to the development of painful contractures, increases patients' risk for repeat injuries, and limits their ability to return to a baseline or pre-injury level of function. The development of successful therapies for these injuries must consider the pathophysiology of these musculoskeletal conditions. We discuss the direct use of muscle-derived stem cells and some key cell population dynamics as well as the use of clinically applicable modalities that may enhance the local supply of stem cells to the zone of injury by promoting angiogenesis.