Alcohol-associated life-style disease, as exemplified by alcoholic liver disease (ALD), is multifactorial with intricate interactions among genetic and environmental factors predicating individual predisposition. To experimentally dissect the interfaces of these interactions for better understanding of the pathogenesis, it is essential to have an animal model that provides maximal control over ethanol and dietary intake and that enables a precise addition or deletion analysis for a risk or protective factor of interest. Rodent intragastric ethanol infusion (IEI) model was developed two decades ago to meet this requirement. Work conducted with the model to date demonstrates the importance of both maximal ethanol intake and secondary risk factors in ALD. Mouse IEI model proved to be particularly useful for genetic analysis of the ALD pathogenesis and has the potential of producing synergistic pathologic outcome by combination of risk factors. The model is best used by alcohol researchers through a center-supported core facility and its tissue sharing program.