Forty-eight million Americans smoke because of addiction to nicotine, and prevention of smoking initiation and new methods for aiding in smoking cessation are some of the most important opportunities for disease prevention available (1). This smoking addiction results from nicotine acting on neuronal nicotinic acetylcholine receptors (nAchRs) in the brain in key regions controlling behavior. There is detailed structural and functional information on neuronal nAchRs that are the prototype of ligand-gated ion channels mediating transmission of endogenous acetylcholine (Ach) and exogenous nicotine signals in the central and peripheral nervous system (2). In addition to the well-formulated role of nAchRs in the etiology of addiction, emerging evidence suggests that nicotine contributes directly to lung carcinogenesis through stimulation of nAchRs in non-neuronal cells. Our group showed that many lung cancers expressed nAchRs and that low concentrations of nicotine blocked the induction of apoptosis in these cells (3). Conti-Fine’s group demonstrated that functional nAchRs are expressed in human and rodent bronchial epithelial cells (4, 5). While not in the bronchial epithelium, Grando and colleagues showed that human epidermal keratinocytes synthesize, secrete, and degrade Ach which is used to mediate stimulation of calcium influx and cell differentiation through α7 nAchRs on these same cells (6, 7). nAchRs bind not only nicotine, but also nicotine-derived nitrosamines such as the tobacco specific carcinogens N′-Nitrosonornicotine (NNN) and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which are potent lung carcinogens. There is evidence from Schuller’s group that lung cancer and fetal pulmonary neuroendocrine cells express nAchRs that bind these ligands with higher affinity than nicotine stimulating the growth of these cells (8–10).