The study of cytokeratin expression has provided a valuable insight into the biliary microanatomy of the liver in health and disease. The canals of Hering are a putative site of origin for progenitor cells, which may repopulate the liver after cellular damage and loss. Normal bile ducts and the bile ductular reaction that occurs in many chronic liver diseases - especially chronic biliary tract disease - express cytokeratin (CK) 7 and CK19. Therefore, both ductopenia and the process of bile ductular reaction can be highlighted with immunohistochemistry for these cytokeratins. Furthermore, CK7 is usually expressed in an increasingly widespread manner by hepatocytes as chronic cholestatic liver disease progresses. For these reasons, CK immunohistochemistry is a very useful adjunct to morphological assessment and histochemical stains for copper retention when a diagnosis of chronic biliary disease is being considered. This review describes the anatomical theory behind the use of CK immunohistochemistry for the assessment of bile duct number and distribution in the liver and provides practical advice for the application of this technique in the diagnostic setting of common medical liver diseases.