Alcohol, the most widely used psychoactive drug worldwide, is a major contributor to premature death among people aged 15 to 49 years, driven by patterns of excessive and harmful use (1). Establishing clear criteria for defining the dose of alcohol consumed —considering the complexity of alcoholic beverages—and understanding its metabolic fate after ingestion are critical steps for estimating exposure to the brain and other organs and predicting the behavioral and toxic effects of alcohol use. Given its importance to human health, several excellent reviews on alcohol metabolism have been published over the last two decades (2–6). In this review, we explore the origins of alcohol use by humans and its metabolism and provide an update on the state of the science of pharmacokinetics, that is, the absorption, distribution, metabolism, and excretion of alcohol. We highlight recent advances in the understanding of the systemic and central metabolism of alcohol, including the discovery of regional expression of key alcohol metabolism enzymes and their genetic variants. Special attention is given to the modulating effects of biological sex, fed state, reproductive status of women,
