Injection of platelet-rich plasma (PRP) is an evolving treatment option for various musculoskeletal injuries. There is basic scientific evidence that suggests that the various growth factors present in PRP can help to augment the body's natural healing. There are also clinical studies suggesting efficacy for several conditions, particularly tendinopathy and osteoarthritis. This article reviews the definition and first uses of PRP, the basic scientific rationale for its use, and the basic science and evidence for its use in the treatment of tendon, joint, ligament, and muscle injuries. There are varying levels of evidence for and against the use of PRP for these types of injuries, and this article reviews studies that support as well as studies that refute the use of this new treatment. There are several studies that have assessed the basic science supportive of PRP treatments, as well as the clinical efficacy of this treatment in vivo. While the current evidence is mixed, several recent studies have demonstrated therapeutic benefit in the treatment of various tendinopathies and degenerative joint diseases of the knee. There are several factors that need to be addressed to elucidate whether PRP is truly effective. These include fully defining the PRP mixture (e.g. concentration, growth factor levels, presence of white cells and red cells, etc.), determining the optimal preparation and delivery of the PRP graft, calculating the appropriate number of injections for each specific pathologic process, and defining optimal post-procedure rehabilitation.