The clinical, radiological and pathological features of acute necrotizing encephalopathy of childhood, a disease entity established recently, are described. This disease predominantly affects infants and young children living in Japan and Taiwan, and manifests itself as acute encephalopathy following viral infections. The hallmark of this encephalopathy is multifocal, symmetric brain lesions affecting the bilateral thalamus, brainstem tegmentum, cerebral periventricular white matter and cerebellar medulla, which can be visualized by computed tomography and magnetic resonance imaging. Both the gray and white matter are involved, with neuropathological evidence of local breakdown of the blood-brain barrier (dysoria). The prognosis was poor in the 1980s, but has improved recently. A characteristic combination of focal neurologic signs is often recognized as the sequelae. Its distinction from clinically similar conditions, such as the Reye syndrome, and from pathologically related conditions, such as the Leigh and Wernicke encephalopathies, is also discussed.