Circulating osteogenic precursor (COP) cells are blood-borne cells that express a variety of osteoblastic markers and are able to form bone in vivo. Strong evidence suggests that COP cells are derived from bone marrow and are of hematopoietic origin. The study of COP cells has been limited by several factors, including the difficulty in establishing long-term cultures and lack of a standardized protocol for their isolation and identification. However, experimental evidence supports that COP cells seed sites of injury and inflammation in response to homing signals and are involved in processes of pubertal growth, fracture, and diverse conditions of heterotopic bone formation. The role of COP cells in physiologic and pathophysiologic conditions of de novo bone formation suggests that they may serve as future targets for diagnostic measurements and therapeutic interventions.