Ethanol consumption causes fatty liver, which can lead to inflammation, fibrosis, cirrhosis and even liver cancer. The molecular mechanisms by which ethanol exerts its damaging effects are extensively studied, but not fully understood. It is now evident that nuclear receptors (NRs), including retinoid x receptor α and peroxisome proliferator-activated receptors, play key roles in the regulation of lipid homeostasis and inflammation during the pathogenesis of alcoholic liver disease (ALD). Given their pivotal roles in physiological processes, NRs represent potential therapeutic targets for the treatment and prevention of numerous metabolic and lipid-related diseases including ALD. This review summarizes the factors that contribute to ALD and the molecular mechanisms of ALD with a focus on the role of NRs.