In the past, the terms hypoxic-ischemic encephalopathy (HIE) of the newborn and perinatal asphyxia have been used, rather loosely, as synonyms. In reality, establishing a clear relationship between perinatal brain injury and ischemia/hypoxemia is often difficult. In the immediate newborn period, many factors can produce neurologic symptoms mimicking those of HIE, including prepartum and postpartum ischemia/hypoxemia, genetic factors, metabolic disease, and maternal and fetal drug use. Sarnat staging oF HIE is useful. Drugs and other conditions that may produce neonatal neurologic alterations similar to those of HIE should be excluded.