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Delirium is a widespread and serious but under-recognized problem. Increasing evidence argues that emergency health care providers need to assess the mental status of the patient as the “sixth vital sign”. A simple, sensitive, time-efficient, and cost-effective tool is needed to identify delirium in patients in the emergency department (ED); however, a stand-alone measurement has not yet been established despite previous studies partly because the differential diagnosis of dementia and delirium superimposed on dementia (DSD) is too difficult to achieve using a single indicator. To fill up the gap, multiple aspects of a case should be assessed including inattention and arousal. For instance, we proposed the 100 countdown test as an effective means of detecting inattention. Further dedicated studies are warranted to shed light on the pathophysiology and better management of dementia, delirium and/or “altered mental status”. We reviewed herein the clinical questions and controversies concerning delirium in an ED setting.