Serotonin syndrome is a toxic condition due to serotoninergic hyperstimulation, which is caused mostly by serotonergic agents either in overdose or in combination. The diagnosis is purely clinical and poorly validated. We described a patient with tremor, mydriatic pupils, clonus, and ataxia after a single dose of duloxetine; on the dosage of admission. Duloxetine belongs to a large class of antidepressants called reuptake inhibitors. The case is presented to emphasize this possible toxicity due to increasing availability of serotonergic agents. It is a complex but easily preventable and recognizable condition. We believe this to be one of the rare reports of serotonin syndrome associated with duloxetine.