Purpose of Review Overview the outcomes of the latest use of platelet-rich plasma (PRP) for the treatment of knee lesions in the clinics and discuss the challenges and limitations. Recent Findings Recent clinical studies mainly indicate there may be benefit of PRP usage for the treatment of knee lesions. As an autologous source of bioactive components, PRP has been shown to be typically safe, free of major adverse outcomes. The use of PRP has been continuously increasing, and some well-designed, double-blinded, placebo-controlled clinical trials have been published. Summary Clinical outcomes relating to PRP usage are multifactorial and depend on the severity of the lesion and patient characteristics. Although PRP is safe to use and it can be easily applied in the clinics, case-specific considerations are needed to determine whether PRP could be beneficial or not. If the use of PRP is favored, then, the configuration/optimization of the preparation and administration/delivery strategy with or without a concomitant treatment may further enhance the clinical outcomes and patients’ experience.