Emergency department physicians are frequently called upon to assess patients with altered mental status. This can be a daunting task for even the most experienced provider because altered mental status is the final common pathway for numerous structural and functional disorders. A rapid but thorough history, physical, and neurologic examination will generally provide insight into the underlying problem. This article provides an algorithm for evaluating these difficult patients followed by specific neurologic examination pearls. This article also reviews the common etiologies for altered mental status.