Examination of the pharmacokinetics of acetaminophen can decrease misconceptions involved in clinical evaluation. Enzyme patterns and acetaminophen levels must be related to time and known metabolic phenomena. A careful look at ethanol and nutrition, especially fasting demonstrates that therapeutic doses of acetaminophen do not place patients at a greater risk in either of these instances. An overdose of acetaminophen in a chronic alcohol abuser may result in more severe hepatotoxicity than in the nonalcoholic. CYP2E1 and glutathione must be evaluated simultaneously rather than in isolation. Glucuronidation capacity in humans is not a factor except in massively overdosed patients. (HEPATOLOGY 2004;40:10–15.)