Sustained release bupropion (amfebutamone) is a non-nicotine agent that is indicated as an aid to smoking cessation. In 2 large well designed clinical trials, sustained release bupropion 300 mg/day (the recommended dose) for 7 or 9 weeks was associated with considerably and significantly higher smoking abstinence rates (continuous abstinence and 7-day point prevalence rates) than placebo during treatment and at follow-up at 6 and 12 months. Point prevalence rates at 12 months in 2 studies were 23.1 and 30.3% with bupropion, whereas values for placebo were 12.4 and 15.6%. Continuous abstinence rates at 12 months, available from 1 trial, were 18.4% with bupropion and 5.6% with placebo. Furthermore, bupropion was associated with significantly higher quitting rates than nicotine patch in a comparative study. Combination therapy with bupropion and nicotine patch provided slightly higher abstinence rates than bupropion alone, although differences were not statistically significant. The combination was superior to nicotine patch alone. Data from a preliminary report of long term bupropion treatment (52 weeks) showed that the drug was associated with significantly higher continuous abstinence rates than placebo only to 6 months. However, point prevalence abstinence rates were significantly higher with bupropion than placebo to 18 months. Bupropion 300 mg/day recipients reported nicotine withdrawal symptoms during treatment; however, the symptoms were significantly less severe with bupropion than placebo. Patients receiving bupropion 300 mg/day or bupropion in combination with nicotine patch for smoking cessation generally gained less bodyweight than placebo recipients. The benefits of bupropion for preventing weight gain persisted after the completion of long term, but not short term therapy. Bupropion was well tolerated in clinical trials, and the only adverse events that were significantly more common with bupropion than placebo were insomnia and dry mouth. Data published so far suggest that sustained release bupropion has a low potential for inducing seizures (seizure rate approximately 0.1% in patients with depression). Conclusions: Bupropion is an effective and well tolerated smoking cessation intervention. Further studies with long term follow-up will be useful in determining whether abstinence rates are maintained with bupropion. In addition, clarification of its efficacy in comparison with other therapies used for smoking cessation would help to establish its clinical value. The reduced potential for weight gain with bupropion and the ability to use bupropion in combination with nicotine replacement therapy make the drug a useful treatment option for smoking cessation.