Bupropion hydrochloride, an atypical antidepressant, is the first non-nicotine product that, in its sustained release form (bupropion SR), has been licensed as an aid for smoking cessation. The specialized literature on bupropion SR and smoking cessation is critically reviewed. The pharmacological profile, dosage and administration, contraindications, as well as the clinical efficacy, safety and tolerability data of bupropion are discussed. Recent reports suggest that its mode of actions might be different to what had originally been proposed. When prescribed appropriately, it appears to be a safe, well-tolerated and effective medication in combination with smoking cessation counselling–for a wide range of smokers, as shown in several multicentre double-blind, placebo-controlled clinical trials. Further research is needed on aspects such as the optimal duration of treatment, the potential role of combination therapy with NRT and psychological interventions, and to establish its effectiveness in smokers with other psychiatric disorders or when used with only minimal support by general practitioners.