The healing of a muscle injury is a complex and dynamic process characterized by different overlapping phases resulting in the restoration of the anatomic continuity and function. This process, triggered by the tissue injury itself, is modulated by different growth factors capable of directing the recruitment, duplication, activation, and differentiation of different cell types. This key role played by different growth factors is the basis of the use of platelet-rich plasma in several circumstances, all of them characterized by the need of activating or ameliorating the process of tissue repair. There is an extensive documentation of in vitro and in vivo studies demonstrating the safety and efficacy of growth factors in the muscle healing process. Unfortunately, for many different reasons, experimental results are usually difficult to interpret, clinical results are controversial, and the relevance of use is still debatable. The present article aims to review the available scientific literature with particular focus on actual clinical applications.