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The liver, perhaps because of its crucial role in metabolism and detoxification of many potentially hazardous xenobiotics, has evolved not one but three stem cell populations. The one that usually operates is the hepatocyte population itself. Hepatocytes were formerly (and incorrectly) considered to have a limited division potential because only 2–3 rounds of cell division occurred after a two thirds partial hepatectomy but this was all that was required to restore liver mass! However, their full division potential has been unmasked through the study of models of hepatocyte transplantation, and they fully deserve the appellation of “functional stem cells” with at least some of them being capable of in excess of 100 divisions. A second population comes into play when either hepatocyte regeneration is compromised after injury or when parenchymal damage is particularly severe. If we did not already know it, rats and humans are different and this extends to the intrahepatic biliary tree. In rats, the terminal bile ductules (canals of Hering) barely extend beyond the portal tract, and the so-called ductular oval cell response that occurs after parenchymal injury when hepatocyte regeneration is inhibited emanates from …