Altered mental status (AMS) and coma are terms used to describe disorders of arousal and content of consciousness. AMS may account for up to 4% to 10% of chief complaints in the emergency department setting and is a common accompanying symptom for other presentations. AMS is not a diagnosis, but rather a term for symptoms of acute or chronic disordered mentation, including confusion, disorientation, lethargy, drowsiness, somnolence, unresponsiveness, agitation, altered behavior, inattention, hallucinations, delusions, and psychosis. Some of the most common disorders associated with AMS are underlying medical conditions, substance use, and mental disorders. This document focuses on the appropriateness of neuroimaging in adult patients presenting with AMS changes including new onset delirium or new onset psychosis. In these cases, imaging is often expedited for initial stabilization and to exclude an intracranial process requiring intervention. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.