Tobacco dependence is the leading cause of preventable death and disability in the United States. While smoking prevalence among U.S. adults is 19.3%, the prevalence of smoking among methadone-maintained patients ranges between 73.5% and 94%. Most methadone-maintained smokers (76%-80%) desire to quit smoking; however only a minority of these smokers receive cessation treatment or referrals for smoking cessation intervention. Smoking cessation treatment in methadone-maintained patients has generally been successful in reducing the daily number of cigarettes smoked. Unfortunately, sustained cessation rates using nicotine replacement therapy and behavioral interventions have generally been low (0%-11%). Poor cessation outcomes may be partially explained by pharmacodynamic interactions between nicotine and methadone leading to increased reinforcement of smoking behavior. Further research is needed to improve smoking cessation rates in methadone-maintained patients.