Bupropion is an atypical antidepressant agent approved for treating major depressive disorders and prescribed for smoking cessation, attention deficit hyperactive disorder (ADHD), and sexual dysfunction. In a few cases, bupropion was associated with myoclonus. We present a case of a 58-year-old male, a heavy smoker seeking smoking cessation, was prescribed bupropion 150 mg twice daily. The subject doubled the dosage without medical advice. After 3 days of the increased dosage, he started to experience abnormal movements in his upper limbs associated with diffuse facial twitching. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Bupropion was discontinued, and clonazepam was initiated. The subject fully recovered within 24 hours. To the authors’ knowledge, only 8 cases of bupropion-induced myoclonus were reported in the literature. Bupropion discontinuation was the most common management. All individuals except 2 cases fully recovered after bupropion withdrawal. The mechanism of bupropion is probably associated with the serotoninergic pathway.