Platelet-rich plasma (PRP) has become an increasingly utilized biological adjunct in orthopedics, particularly in sports medicine. Cartilage repair is one such application for which PRP has been utilized. Osteochondral lesions of the talus are common athletic injuries, and they present a difficult clinical problem in part because of the poor biological environment of cartilage healing. The current authors’ are investigating the use of PRP with reparative and restorative techniques, including arthroscopic bone marrow stimulation and autologous osteochondral transplantation, respectively. The hypothesis is that the bioactive molecules and growth factors contained within PRP will stimulate a healing response for the differentiation of fibrocartilage such that it resembles a more hyaline-like microstructure, in addition to enhancing bony incorpoaration. In addition to these anabolic pathways, there is also recent evidence to suggest that PRP may inhibit the catabolic processes of arthritis. This article presents the indications and treatment strategy for using PRP in the surgical treatment of osteochondral lesions of the talus.