Children and adolescents are increasingly presenting to the hospital and emergency department with aggressive behavior and psychiatric emergencies. The rise in pediatric mental health problems, coupled with a lack of much needed resources, necessitates that pediatricians safely diagnose and treat patients presenting with aggressive behavior. In this article, we discuss the broad differential diagnosis that should be considered when initially evaluating a patient presenting with aggression or altered mental status; underlying causes include predisposing factors, comorbid conditions, and acute organic causes involving almost every organ system. Emergency and hospital physicians should tailor their examination and testing individually based on the patient's history and presentation. [ Pediatr Ann. 2018;47(10):e402–e407.]

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