At present, there is no rational approach in the management of hypoxic-ischemic encephalopathy. In the past, therapies directed toward decreasing cerebral edema were used to prevent or to reduce the severity of hypoxic-ischemic encephalopathy. However, investigations in both experimental animals and humans have showed that these drugs have little efficacy in the management of the asphyxiated fetus or newborn. Since there is no effective management of perinatal hypoxic-ischemic encephalopathy, the investigators have to sight new approaches for the prevention and treatment of the asphyxiated fetus or newborn. Several pharmacologic agents currently undergo intense investigation for this purpose.