Cigarette smoking is common among persons with alcohol dependence or abuse with as many as 80% of persons who are alcohol dependent also being smokers. Not only is smoking common in persons with heavy alcohol consumption, but also nicotine dependence appears more severe in smokers with a history of alcohol dependence. This combined exposure to both tobacco smoke and alcohol results in major health consequences including additive risks for some diseases such as head and neck cancers. Although modest alcohol consumption has some positive health benefits, smoking typically negates these benefits. The cellular mechanisms impacted by combined smoking and alcohol exposure are poorly understood, but molecular epidemiology approaches are providing insights regarding the importance of effects on oxidant/antioxidant pathways and on metabolic pathways involving the cytochrome P450 system. Given the prevalence of smoking in the alcohol dependent population, smoking cessation in this group has the potential for tremendous impact. In recent years, smoking cessation approaches have been initiated in this population, but much work remains in order to define the optimal smoking cessation strategies for persons in alcohol treatment programs.