Agitation is a chief complaint that causes many children and adolescents to present to emergency medical attention. There are many reasons for acute agitation, including toxicologic, neurologic, infectious, metabolic, and functional disorders. At times it may be necessary to pharmacologically treat the agitation to prevent harm to the patient, caregivers, or hospital staff. However, one should always be mindful that the differential diagnosis is broad, and a complete although timely assessment with targeted testing must be done before concluding that the agitation is rooted solely in nonorganic causes. There are various pharmacologic choices for the treatment of agitation, and they will be reviewed here. While treatment of agitation may be necessary to keep the patient as well as staff safe, as well as to facilitate medical evaluation in some cases, care must be taken to treat the patient with compassion, never using pharmacologic treatment for reasons of punishment or staff convenience. The focus is on the pharmacologic management of acute agitation of patients in the pediatric age group, in the context of a full evaluation for possible nonfunctional causes of agitation. Goals, risks, and benefits of medication use will be reviewed. © 2014 by Lippincott Williams & Wilkins.