The clinical presentation is classically described as a triad of cognitive/behavioral changes (confusion, agitation, lethargy, coma), autonomic instability (hyperthermia, tachycardia, diaphoresis, nausea, vomiting, diarrhea, dilated pupils), and neuromuscular changes (myoclonus, hyperreflexia, rigidity, trismus) [13]. It is known to vary on a spectrum ranging from mild to moderate to severe including death [2]. Several sets of diagnostic criteria have been developed to define serotonin syndrome, including the Sternbach criteria [2] and the Hunter Criteria [14] (Box 9.1). In a study of the Hunter Criteria , the clinical findings that have been shown to have a statistically significant association were clonus (inducible, ocular, spontaneous), myoclonus, hyperreflexia, peripheral hypertonicity, and shivering [14]. The onset of symptoms is typically rapid; approximately 75% of patients with serotonin syndrome present within 24 h after initial use of medication, an overdose, or a change in dosing [13]. However, administration of a serotonergic agent within 5 weeks after the discontinuation of fluoxetine has been shown to initiate serotonin syndrome [15]. It does not resolve spontaneously unless the causative agents are discontinued.