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This chapter reviews evidence supporting the hypothesis that genetic inheritance plays a substantial role in dependence on cocaine and (to a less well-studied degree) other illicit psychostimulants. The role of genes in cocaine dependence, however, may largely reflect a more general liability to develop dependence on a variety of substances. Studies of molecular genetic mechanisms in cocaine dependence remain in an early stage of development. A genome-wide association study (GWAS) of methamphetamine dependence, while yielding some interesting leads, requires replication in light of its small size, and reliance on pooled genotyping. While several intriguing candidate-gene associations between specific loci and cocaine dependence have been reported, to date there has yet to be a definitively replicated result reported. Clearly, more work is required in the human genetics of stimulant dependence, to identify and characterize how specific genes influence risk for this set of disorders.