Drug dependence is a chronic brain disease characterized by recurrent episodes of relapse, even when the person is motivated to quit. Relapse is a major problem and new pharmacotherapies are needed to prevent relapse episodes. The nicotinic acetylcholine receptor (nAChR) plays an important role in nicotine dependence, alcohol consumption and cue-induced cocaine craving. Stimulation of the nAChR has been found to alter and modulate cell firing in brain areas important for the maintenance of drug dependence. Varenicline, an alpha4beta2 nAChR partial agonist and an alpha7 nAChR full agonist registered for the treatment of nicotine dependence, significantly reduces nicotine craving and prevents relapse. In addition, varenicline reduces alcohol consumption in rats. Based on a review of the available literature, we hypothesize a potential role for varenicline in the prevention of relapse in patients recovering from drug dependence other than nicotine dependence.