Altered mental status is a sign of serious neurologic or systemic disease. The physician must rapidly assess the depth of coma and risk of intracranial hypertension, then determine the etiology and prescribe appropriate management. This is no small task, considering the variety and multitude of illnesses that may present with altered mental status. The etiologies can be broken down into structural and medical causes. The structural causes more frequently affect the brainstem centers adjacent to the ascending reticular activating system that are responsible for pupillary response and oculocephalic reflexes. Medical causes generally spare these structures. Management of structural lesions requires prompt diagnosis and neurosurgical input. Medical etiologies are protean and treatment is often supportive.