Alcohol dependence is a common, complex disorder, which affects millions of people worldwide and causes considerable burden in terms of interpersonal and societal costs. Family, twin, and adoption studies have convincingly demonstrated that genes play an important role in the development of alcohol dependence, with heritability estimates in the range of 50% to 60% for both men and women. A number of studies are under way to identify specific genes involved in the predisposition toward alcohol dependence, and there is reason to be enthusiastic about recent progress. Several associated susceptibility genes are reviewed here, including genes involved in alcohol metabolism, as well as genes involved in GABAergic, endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission. The next challenge will be to further characterize the risk associated with these susceptibility genes, examining how they may be related to comorbid disorders, developmental trajectories of risk, and potential moderation by environmental factors.