This article reviews current concepts on the pathogenesis and treatment of alcoholic liver disease. It has been known that the hepatotoxicity of ethanol results from alcohol dehydrogenase-mediated excessive generation of hepatic nicotinamide adenine dinucleotide, reduced form, and acetaldehyde. It is now recognized that acetaldehyde is also produced by an accessory (but inducible) microsomal pathway that additionally generates oxygen radicals and activates many xenobiotics to toxic metabolites, thereby explaining the increased vulnerability of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over-the-counter medications, and carcinogens. The contribution of gastric alcohol dehydrogenase to the first-pass metabolism of ethanol and alcohol-drug interactions is discussed. Roles for hepatitis C, cytokines, sex, genetics, and age are now emerging. Alcohol also alters the degradation of key nutrients, thereby promoting deficiencies as well as toxic interactions with vitamin A and beta carotene. Conversely, nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other "supernutrients" include polyunsaturated lecithin, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in nonhuman primates. Thus, a better understanding of the pathology induced by ethanol is now generating improved prospects for therapy.