Alcohol metabolism is one of the biological determinants that can significantly influence drinking behavior and the development of alcoholism and alcohol-induced organ damage. Most ethanol elimination occurs by oxidation to acetaldehyde and acetate, catalyzed principally by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Other ethanol oxidation pathways, including catalase and microsomal ethanol-oxidizing system (MEOS/CYP2E1), as well as the nonoxidative pathway (FAEES), which forms fatty acid ethyl esters, appear to play a minor role. The major alcohol metabolizing enzymes exhibit genetic polymorphism and ethnic variation. In this review recent advances in the understanding of the functional polymorphisms of ADH, ALDH and CYP2E1 and their metabolic, physiologic and clinical correlations are presented.