The serotonin syndrome is a complication of serotonergic medications that is being recognized with increasing frequency in both adults and children. Patients present with a constellation of mental status change, autonomic instability, and increased neuromuscular tone. Symptoms can include tremor, hyperreflexia, and clonus, typically in the lower extremities. The syndrome is caused by stimulation of a subset of serotonin receptors in the brainstem and spinal cord. Most cases are exposed to multiple serotonergic medications, such as selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. Certain drugs of abuse, analgesics, antibiotics, and herbal medications have been recently associated with the serotonin syndrome. Diagnosis is based on clinical presentation and exposure to serotonergic medications, although other causes of mental status change usually need to be excluded. Management includes discontinuation of the offending agent and supportive care, whereas targeted therapy with serotonin antagonists, such as cyproheptadine, can help confirm the diagnosis and relieve symptoms.