Due to the adverse health consequences related to smoking, it is important to understand factors that contribute to nicotine dependence. The most replicated genetic finding for nicotine dependence points to variants on chromosome 15, which includes the α5-α3-β4 nicotinic receptor gene cluster. A compelling functional variant is a polymorphism, rs16969968, which alters an amino acid in the α5 nicotinic receptor subunit. Several prominent studies report that the replicated nicotine dependence locus also influences the risk for lung cancer and chronic obstructive pulmonary disease. This represents an exciting convergence of genetic findings, and highlights the potential for research on smoking to inform public health.