Skeletal muscle performs multiple functions in the body including locomotion, maintenance of body temperature, energy storage, and as a secretory organ. Skeletal muscle has a considerable capacity for regeneration in response to injury through the resident stem cells populations that present in skeletal muscle. To study skeletal muscle regeneration in a controlled and reproducible approach, it is crucial to develop an experimental animal model with a stable skeletal muscle injury. These injury models increase our knowledge about the cellular, as well as the molecular signaling pathways that occur during both the degeneration and regeneration stages. Such knowledge will help to develop new therapeutics for treating congenital and acquired myopathies. There are several experimental models to study muscle regeneration in vivo, these models include chemical, physical, surgical, and ischemic. The nature of the injury affects the cellular events of muscle degeneration and regeneration, as well as their time course. Therefore, it is crucial for researchers to carefully choose the suitable injury model according to the experimental design, as well as the expected outcomes.