Serotonin syndrome is an acute, potentially life-threatening drug reaction caused by excess serotonin activity. The RN plays a critical role in early recognition, reporting, and implementing emergency interventions. The classic presentation is a clinical TRIAD: (1) mental status changes (agitation, anxiety, confusion, delirium), (2) autonomic dysfunction (tachycardia, hypertension, diaphoresis, hyperthermia, mydriasis, diarrhea), and (3) neuromuscular abnormalities (clonus — the hallmark, hyperreflexia, tremor, myoclonus, rigidity in severe cases). Onset is typically RAPID — within hours of medication change. The most important bedside assessment is testing for clonus: briskly dorsiflex the patient's ankle and observe for sustained rhythmic contractions. Clonus distinguishes serotonin syndrome from NMS. Treatment centers on: (1) removing the offending serotonergic agent, (2) benzodiazepines for agitation and muscle hyperactivity, (3) cyproheptadine (serotonin antagonist) for moderate-severe cases, and (4) aggressive cooling and supportive care for severe hyperthermia.