Cartilage injuries of the knee are common among professional athletes. The variety, limited regenerative capabilities, and possible secondary degenerative effects as well as associated injuries make this kind of injury difficult to address. Depending on lesion size, location, or chronicity, multiple (non)operative therapies are available, each requiring a unique return-to-activity (RTA) protocol. Unfortunately, there is no evidence-based consensus on this process. Nowadays, rehabilitation after cartilage injuries of the knee is based on a few principles (joint protection and careful activation, progressive joint loading and function restoration, and restoration of activity) which need individual experience-based adaptation. Despite general high RTA rates of 75–90% at usually 6–12 months after therapy, depending on the treatment method, an optimal RTA strategy remains challenging. The multiplicity of different variables together with missing consensus do not guarantee a certain result and hinder setting the best possible and safe return to high-level activity. Since there are no unambiguous recommendations, every single RTA should be evaluated individually, considering athletes’ and injury-specific factors. Unfortunately, there is still missing evidence to make it possible to provide any “gold standards” or accurate numbers in this process. This chapter summarizes up-to-date recommendations in terms of RTA after cartilage therapy of the knee.