The molecular processes that underlie addiction are beginning to unfold. Genetically determined variations in dopaminergic neurotransmission predispose to nicotine dependence. In addition, tobacco use is likely to be governed by the rate at which smokers metabolize nicotine. Functional polymorphisms in CYTOCHROME P450 monooxygenases that metabolize nicotine have now been defined and it should soon be possible to identify fast nicotine metabolizers by DNA analysis. Here, we review the key neurotransmitter receptors and metabolic enzymes implicated in tobacco dependence. We explore the potential benefits of classifying smokers according to the molecular aetiology of their habit. One major benefit will be in planning effective strategies for smoking cessation. Methods of typing for alleles related to smoking behavior that might be suitable for use in clinical practice in the future will also be discussed