Hamstring strain injuries are common among sports that involve sprinting, kicking, and high-speed skilled movements or extensive muscle lengthening-type maneuvers with hip flexion and knee extension. These injuries present the challenge of significant recovery time and a lengthy period of increased susceptibility for recurrent injury. Nearly one third of hamstring strains recur within the first year following return to sport with subsequent injuries often being more severe than the original. This high re-injury rate suggests that athletes may be returning to sport prematurely due to inadequate return to sport criteria. In this review article, we describe the epidemiology, risk factors, differential diagnosis, and prognosis of an acute hamstring strain. Based on the current available evidence, we then propose a clinical guide for the rehabilitation of acute hamstring strains and an algorithm to assist clinicians in the decision-making process when assessing readiness of an athlete to return to sport.