Advances in neuroimaging and genomics provide an unprecedented opportunity to accelerate medication development for nicotine dependence and other addictions. Neuroimaging studies have begun to elucidate the functional neuroanatomy and neurochemistry underlying effects of nicotine and nicotine abstinence. In parallel, genetic studies, including both candidate gene and genome-wide association approaches, are identifying key neurobiological targets and pathways important in addiction to nicotine. To date, only a few neuroimaging studies have explored effects of nicotine or abstinence on brain activity as a function of genotype. Most analyses of genotype are retrospective, resulting in small sample sizes for testing effects of the minor alleles for candidate genes. The purpose of this review is to provide an outline of the work in neuroimaging, genetics, and nicotine dependence, and to explore the potential for increased integration of these approaches to improve nicotine dependence treatment.