Acute necrotizing encephalopathy of childhood (ANE) is a clinicopathological entity recently separated from acute encephalopathy of unknown etiologies. The hallmark of ANE is multiple, bilateral symmetric brain lesions showing edema and necrosis which occur in the bilateral thalami and other specific regions. Since its establishment in 1993-1995, data have further accumulated and have provided additional insight into its pathogenesis. This review summarizes recent achievements on ANE, with reference to issues to be clarified by future studies.