In the natural course, about 30 % of patients with focal cartilage defects of the medial knee compartment undergo rapid OA progression (arthroplasty as end-stage of the disease). There are general risk factors (age, female gender and obesity) but also local risk factors. Furthermore, tibial defects and the extent of meniscus loss influence the outcome significantly. These general and local factors should be more carefully estimated or addressed in future clinical and scientific work.