Current treatment principles of muscle injuries have either been derived from experimental studies or been tested only empirically. Although nonoperative treatment results in good functional outcomes in the majority of athletes with muscle injuries, the consequences of failed treatment can be very dramatic, possibly postponing an athlete’s return to sports for weeks or even months. Moreover, the recognition of some basic principles of skeletal muscle regeneration and healing processes can considerably help in both avoiding the imminent dangers and accelerating the return to competition. Accordingly, in this review it is summarized the prevailing understanding on the biology of muscle regeneration. Many prospective studies have shown that the previous injury is the greatest risk factor of sustaining the injury. However the primary causes of the injury are unclear in soccer. A lack of hamstring flexibility has been one of the main injury risk factors. Running is often identified as the primary activity type for hamstring injury and given the high eccentric forces and moderate muscle strain placed on the hamstrings during running these factors are considered to be part of the aetiology of hamstring injury. However, the exact causes of hamstring injury remain unknown and whilst eccentric contraction and muscle strain purportedly play a role, accumulated muscle damage may also contribute. Potentially, all of these factors interact to varying degrees depending on the injurious activity type (i.e. running, kicking). Furthermore, anatomical factors, such as the biarticular organization, the dual innervations of biceps femoris (BF), fibre type distribution, muscle architecture and the degree of anterior pelvic tilt, have all been implicated. Each of these variables impact upon HSI risk via a number of different mechanisms that include increasing hamstring muscle strain and altering the susceptibility of the hamstrings to muscle damage.