Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. ANE is characterized by a preceding viral illness followed by seizures and rapid progressive neurologic deterioration. The diagnosis of ANE is made based on clinical presentation and characteristic multifocal brain lesions seen on computed tomography (CT). We report a previously healthy two-year-old boy who presented to our emergency department (ED) after a seizure in the setting of fever and diarrhea. He was ultimately diagnosed with ANE and treated with steroids and IVIG. Early identification of this high morbidity condition by its typical clinical picture and characteristic radiologic findings is key to allow for optimal treatment.