In the United States, encounters related to mental and substance use disorders are common in emergency departments (EDs). Altered mental status (AMS) is a frequent presentation seen in EDs across the country. Individuals may present to the ED with altered thought processes, which may be attributed to intoxication from substances and/or psychoses, conditions that require immediate care and management. Health care providers must always ascertain the etiology of AMS, which may be challenging owing to the various causes of this impairment. The current article provides an overview of the most common disorders associated with AMS, which include underlying medical conditions, substance use, and mental disorders. [Journal of Psychosocial Nursing and Mental Health Services, 59(9), 16-25.].