An 84-year-old male with stage III chronic kidney disease and a history of multiple psychiatric and medical disorders presented to the emergency department (ED) with new onset proximal leg weakness with tremor upon standing, truncal ataxia, and myoclonic jerks of the upper extremity that had progressively worsened over three weeks. Magnetic resonance imaging and head computed tomography showed no acute change from baseline. After admission, the patient reported visual hallucinations, vertigo, and slurred speech, and displayed nocturnal agitation/delirium. These symptoms were managed with risperidone. Prior to admission, the most recent medication change was the initiation of bupropion 100 mg extended-release twice daily. Bupropion was titrated to 150 mg twice daily over the three weeks prior to the ED visit. Gradual tapering of the bupropion dose was started after admission. Symptoms of agitation, delirium, speech, and motor disturbances decreased 36 to 48 hours after bupropion dose was lowered to 75 mg daily, and risperidone was changed to quetiapine. The patient was discharged to short-term rehabilitation with return of mental status to baseline. Bupropion and quetiapine were discontinued at discharge from the rehabilitation center. Case reports exist for acute psychotic and parkinsonian symptoms after administration of bupropion and bupropion extended-release, but none exist for the combination of focal neurologic deficits and psychotic symptoms found in this patient's presentation. Limited pharmacokinetic data in the elderly and those with renal impairment suggest that this patient population may have reduced clearance of bupropion. Dose adjustment should be considered in such patients and signs of toxicity closely monitored. Adverse reactions to bupropion should be considered if a patient presents with acute neurologic or psychotic symptoms after initiation or dose modification of bupropion.