A complex interplay of liver, bile ducts, and the gut critically determines functioning of these organs in health and disease. Biochemical and physiological aspects of their interaction and the role of inflammatory cells, cytokines, bile acids, visceral hormones, neuropeptides and other messengers in the pathogenesis of model immune-mediated hepatobiliary disorders are discussed in the actual issue of Clinical Reviews in Allergy and Immunology. Potential molecular targets for future therapeutic approaches are also addressed.