We think that osteonecrosis, to a large degree, develops because of familial and acquired thrombophilia and hypofibrinolysis causing venous thrombosis in the femoral head. We postulate that venous thrombosis leads to increased intraosseus venous pressure, reduced arterial flow, and hypoxic bone death. Many studies suggest that familial and acquired thrombophilia and hypofibrinolysis may play an important etiologic role in adults with osteonecrosis of the hip and jaw and in children with Legg-Perthes disease (pediatric osteonecrosis). We have limited pilot data in adults with osteonecrosis associated with familial thrombophilia and hypofibrinolysis that suggest that 12 weeks of therapy with enoxaparin, if started early (Ficat stages I/II) before femoral head collapse (Ficat stages III/IV), may interrupt the progression of osteonecrosis of the hip. Placebo-controlled trials with a 2-year follow-up or longer in adults will be required to assess the promise of the pilot anticoagulant studies in osteonecrosis.