Cartilage injuries at the ankle joint represent an orthopaedic challenge due to the strong association between joint dysfunction and patient quality of life. Ankle cartilage lesions may be caused by acute trauma, repetitive microtrauma or osteochondral lesions secondary to osteochondritis dissecans of the talus. The lack of regenerative potential of cartilage and its exposure to high mechanical loading hinder treatment and repair. This chapter describes the complex anatomy and biomechanics of the ankle joint and how these factors contribute to vulnerability and poor cartilage healing. It reviews the various methods for diagnosis of osteochondral lesions as well as treatment options, ranging from conservative measures to surgical approaches, including microfracture, autologous chondrocyte implantation and osteochondral grafts. Finally, the chapter addresses exciting advances in tissue engineering and biologic adjuvants, which are highly promising for cartilage regeneration and long-term restoration of joint function. Despite these advances, significant challenges remain regarding achieving native-like repair, warranting continued research for better therapeutic approaches.