Alcohol and nicotine dependence are commonly occurring disorders that together represent the most important preventable causes of morbidity and mortality in the United States. While there have been differences of opinion as to which disorder to treat first when they occur, there is growing evidence that a management strategy addressing both conditions contemporaneously would be optimal. Advances in the neurosciences have demonstrated not only that the reinforcing effects of both alcohol and nicotine are mediated by similar mechanisms resulting in enhanced activity of the cortico-mesolimbic dopamine system, but that their neurochemical interactions can lead to an aggregation of these effects. Despite this striking neurobiological overlap between alcohol and nicotine consumption, few studies have sought to take advantage of this commonality by devising a pharmacological approach that serves to treat both disorders. The results of our proof-of-concept study showed that topiramate is a promising medication for the treatment of both alcohol and nicotine dependence, presumably by its ability to modulate cortico-mesolimbic dopamine function profoundly; however, other mechanisms might also contribute to this effect. Further studies are ongoing to establish and extend topiramate's efficacy in the treatment of each and both disorders. Copyright 2004 Elsevier Ltd.