Cholangiocytes are epithelial cells that line the intra- and extrahepatic biliary tree. They serve predominantly to mediate the content of luminal biliary fluid, which is controlled via numerous signaling pathways influenced by endogenous (e.g., bile acids, nucleotides, hormones, neurotransmitters) and exogenous (e.g., microbes/microbial products, drugs etc.) molecules. When injured, cholangiocytes undergo apoptosis/lysis, repair and proliferation. They also become senescent, a form of cell cycle arrest, which may prevent propagation of injury and/or malignant transformation. Senescent cholangiocytes can undergo further transformation to a senescence-associated secretory phenotype (SASP), where they begin secreting pro-inflammatory and pro-fibrotic signals that may contribute to disease initiation and progression. These and other concepts related to cholangiocyte pathobiology will be reviewed herein. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.