Bile duct damage is present in virtually all cholangiopathies, which share the biliary epithelial cells (i.e. cholangiocytes) as a common pathogenic target. Cholangiocyte cell death largely occurs through the process of apoptosis. In this review, we will summarize the mechanisms through which biliary damage occurs in a variety of animal and in vitro models, such as extrahepatic cholestasis induced by bile duct ligation (BDL), cytotoxin- and hepatotoxin-induced liver injury, and biliary atresia. Although we have increased our knowledge of the factors that regulate cholangiocyte cell death mechanisms during cholangiopathies, especially in experimental models, there is still a lack of effective treatment modalities for these biliary disorders. However, future studies will hopefully provide for new therapeutic modalities for the prevention or restoration of biliary mass and function lost during the progression of cholangiopathies.