Polyploidy has been described in the liver for over 100 years. The frequency of polyploid hepatocytes varies by age and species, but up to 90% of mouse hepatocytes and approximately 50% of human hepatocytes are polyploid. In addition to alterations in the entire complement of chromosomes, variations in chromosome copy number have been recently described. Aneuploidy in the liver is pervasive, affecting 60% of hepatocytes in mice and 30-90% of hepatocytes in humans. Polyploidy and aneuploidy in the liver are closely linked, and the ploidy conveyor model describes this relationship. Diploid hepatocytes undergo failed cytokinesis to generate polyploid cells. Proliferating polyploid hepatocytes, which form multipolar spindles during cell division, generate reduced ploidy progeny (e.g., diploid hepatocytes from tetraploids or octaploids) and/or aneuploid daughters. New evidence suggests that random hepatic aneuploidy can promote adaptation to liver injury. For instance, in response to chronic liver damage, subsets of aneuploid hepatocytes that are differentially resistant to the injury remain healthy, regenerate the liver and restore function. Future work is required to elucidate the mechanisms regulating dynamic chromosome changes in the liver and to understand how these processes impact normal and abnormal liver function. Copyright © 2013 Elsevier Ltd. All rights reserved.