Bupropion is an antidepressant medication with expanding indications including smoking cessation, weight loss, attention-deficit/hyperactivity disorder, seasonal affective disorder, and amphetamine dependence. Despite its increasing popularity among providers, it has a well-known narrow therapeutic window which can lead to delayed onset of symptoms with extended-release formulations and devastating consequences in overdose. We have noticed some patients misusing bupropion via intravenous use and had difficulty guiding decisions regarding clinical monitoring in these patients. As this route entirely changes the kinetics of bupropion, this has caused concern within our group. We reviewed all the cases of intravenous bupropion use reported to a single poison center without any other coingestants. The majority (66.7%) of patients had moderate effects and one patient had a seizure. No deaths were reported. All patients were symptomatic by the time of initial call to the poison center if they had any reported symptoms due to bupropion. This case series describes the clinical effects reported, and the timing of these effects, after intravenous bupropion use.