The application of genomic medicine to the treatment of nicotine dependence holds great promise for revitalizing the steady decline in smoking rates witnessed in the USA over the past several decades. This paper examines the current knowledge base concerning the use of biomarkers to guide the selection of nicotine dependence treatments. First, we review the neurobiology of nicotine dependence and present evidence that supports its heritability. We then discuss the various studies of pharmacokinetic and pharmacodynamic genes related to therapeutic response. Current evidence suggests that biomarkers of genetic variability in both nicotine metabolism, referred to as the nicotine metabolite ratio, and dopamine genotypes may be useful for guiding treatment selection for nicotine dependence. Barriers to the translation of this research to clinical practice are discussed, as are directions for future research.