When youth in the emergency department become acutely agitated, it can be dangerous and distressing to patients, families, and clinicians. Timely, effective, and patient-centered management is key to reducing the potential for patient and staff injury while preserving patient dignity. We review the definition of agitation and pharmacologic management for youth with acute agitation, including common classes of medications, indications for use, and adverse effects. We also discuss the need to integrate the use of medications into a comprehensive strategy for agitation management that begins with proactive prevention of aggressive behavior, creation of a therapeutic treatment environment, and verbal de-escalation strategies.