Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention.