Control of the agitated patient in the emergency department is challenging. Many options exist for chemical sedation, but most have suboptimal pharmacodynamic action, and many have undesirable adverse effects. There are reports of ketamine administration for control of agitation prehospital and in traumatically injured patients. Ketamine is a noncompetitive N-methyl-D-aspartic acid receptor antagonist, making it an effective dissociative agent. We present 5 cases of ketamine administration to manage agitated adolescent patients with underlying psychiatric disease and/or drug intoxication. Ketamine, as a dissociative agent, may be an alternative pharmacological consideration for the control of agitation in patients with undifferentiated agitated delirium.