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Bone graft substitutes are used commonly in orthopedic surgery as an alternative to autograft bone. Autograft bone has the advantages of being osteoconductive, osteoinductive, and osteogenic. However, the quantity of autograft bone available is limited in a given patient and the harvest of autograft bone has been associated with significant morbidity. Bone graft substitutes have become available in an attempt to address these issues and have found widespread use in many areas of orthopedic surgery including sports medicine. The various categories of bone graft substitutes are reviewed here, with an examination of their biologic mechanism of action. Clinical evidence to support their use is also reviewed, with a focus on sports medicine applications.