Abundant evidence from family, adoption and twin studies points to large genetic contributions to individual differences in vulnerability to develop dependence on one or more addictive substances, including tobacco. Twin data suggests that much of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances. Interestingly, some twin data also supports substantial differences in the apparent heritability of nicotine dependence in women as environmental conditions become more permissive for their smoking. In addition, twin studies also support the idea that ability to quit smoking displays substantial heritability, and that this heritable influence overlaps partially with genetic influences on nicotine dependence. Candidate gene molecular genetic studies and genome wide association studies of substance dependence and ability to quit smoking each document apparent polygenic influences that identify lists of genes that display partial overlap, as expected from classical genetic studies. More of these genes are expressed in the brain than would be anticipated by chance. These lists of genes overlap significantly with those identified in molecular genetic studies of individual differences in cognitive abilities, frontal lobe brain volumes as well as personality and psychiatric phenotypes. Though most available genome wide association data do not separate results by gender, it may be notable that few of these genes lie on sex chromosomes. These data provide a substrate to improve understanding of nicotine dependence, the ability to quit smoking, the potential for less permissive environments to restrict the expression of genetic influences on smoking and the possibility that brain features that underlie phenotypes such as individual differences in cognitive abilities might interact with environmental features that are especially prominent for disadvantaged women to provide special circumstances that should be considered in prevention and treatment efforts to reduce smoking.