Patients experiencing acute elevations of ammonia present to the ICU with encephalopathy, which may progress quickly to cerebral herniation. Patient survival requires immediate treatment of intracerebral hypertension and the reduction of ammonia levels. When hyperammonemia is not thought to be the result of liver failure, treatment for an occult disorder of metabolism must begin prior to the confirmation of an etiology. This article reviews ammonia metabolism, the effects of ammonia on the brain, the causes of hyperammonemia, and the diagnosis of inborn errors of metabolism in adult patients.