Cartilage injuries of the ankle are common among professional athletes and can present significant challenges. If left untreated, chondral lesions can predispose individuals to the development of post-traumatic osteoarthritis (OA), which, in severe cases, may lead to the end of an athlete’s career. Consequently, orthobiologic therapies are gaining attention for their potential to reduce symptoms (such as pain during physical activity and impaired joint function), accelerate recovery, and minimize the risk of OA. Recent interest has centered around biologics like platelet-rich plasma and stem cells. However, evidence supporting their effectiveness for ankle cartilage injuries remains limited. While numerous studies report promising results, clinical outcomes remain inconclusive. According to current clinical research, biologic injectable therapies are not routinely recommended for ankle cartilage injuries. Nevertheless, basic and clinical studies over the past two decades have demonstrated that, due to their safety and potential benefits (such as symptom management), orthobiologics can be a viable option for conservative treatment and may offer significant advantages, especially as adjuncts to other interventions. This chapter provides a comprehensive review of the up-to-date evidence on biologic therapies for ankle cartilage injuries.