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In general, ‘drinkers smoke’, and a high proportion of the alcohol-dependent population is also nicotine-dependent. Statistically, the majority of alcoholics will die of smoking-related, rather than alcohol-related, disease. This co-dependent sub-population may have higher levels of nicotine dependence, and find smoking cessation more difficult. Major reasons are that concurrent alcohol use, and/or prior alcohol exposure, may change the reinforcing effects of nicotine, and that each drug becomes a pharmacological cue for the expectation of the other. If so, then smokers whose nicotine dependence is impacted by alcohol, represent a large and distinct sub-population in which both the therapeutic and molecular targets for smoking cessation are altered. This, in turn, has implications for the validity of animal models of nicotine reinforcement, and for the development of novel smoking cessation medications. It is no longer possible to ignore the fact that the two most prevalent and damaging addictive drugs in our society are very commonly used by the same individuals. Without a better understanding of the psychological and pharmacological interactions between alcohol and nicotine that impact dependence, we cannot hope to provide appropriate medications for this large and problematic patient group. Our intention in this opinion overview is to use the current literature to provide a framework for future studies into the impact of alcohol use on the reinforcing effects of nicotine.