Platelet-rich plasma (PRP) has gained significant attention as a potential biological treatment for musculoskeletal conditions, driven by laboratory evidence suggesting that its concentrated growth factors may enhance healing. Despite this enthusiasm, clinical use has expanded faster than supporting evidence, and preparation methods vary widely across systems, producing inconsistent concentrations of platelets, leukocytes, and activating agents. A comprehensive search across major medical databases identified 78 randomized controlled trials—including 5,308 patients—evaluating PRP for a broad range of orthopaedic conditions. Early findings highlight substantial heterogeneity in PRP formulations and study quality, underscoring the need for clearer evidence on when, how, and for whom PRP is effective. Future OE Originals will summarize condition-specific results.