Organ dysfunction is often recognized after exposure to perinatalasphyxia. However, few studies have assessed the pathophysiology andmanagement of hypoxic-ischemic encephalopathy. Little is known aboutthe recent pathophysiologic mechanisms involving mediators and therecent modalities of treatment of hypoxic-ischemic encephalopathy.The aim of this essay is to present the most recent theories ofpathophysiology causing brain damage in hypoxic-ischemicencephalopathy (HIE) as well as recent trends in the managementincluding new therapeutic modalities.