Nicotine plays a major role in lung cancer through smoking addiction. This addiction occurs through nicotine binding to nicotinic acetylcholine receptors (nAChR) in the brain leading to defined brain responses. Nicotine also can be metabolized to carcinogenic forms causing mutations. However, there is now evidence that nicotine can also act directly on lung epithelial and lung cancer cells by binding to nAChRs expressed on these cells. This interaction leads to signaling changes, one of which is activation of the Akt pathway, which in turn leads to increasing antiapoptotic responses in these cells. Thus, nicotine can directly cause lung epithelial and cancer cells to proliferate and to avoid apoptosis. nAChRs are organized into a multimeric structure to provide a ligand-gated ion channel. The components are determined by various nAChR α and β subunits, the composition of which can vary throughout the nervous system and body to give a variety of nAChR types. Lam et al. studied the expression of nAChR subunits in lung cancers arising in smokers compared with never-smokers as well as in normal lung tissue. They found that, besides nAChR subunit expression differences between tumor and normal lung, tumors arising in never-smokers expressed different levels of nAChRs α6β3 subunits compared with those arising in smokers. These results indicate that nicotine plays a role in determining features of lung cancer developing in smokers and suggests nAChRs as targets for prevention and therapy of lung cancer. For details, see the article by Lam et al. on page 4638 of this issue.