Malignancies of the biliary tree are classified into three groups according to location: intrahepatic, central (perihilar), and distal. Of all cholangiocarcinomas, 25% are located distally and can be subdivided into middle and lower bile duct carcinomas. Surgical approaches for achieving tumor-free resection margins (R0) are directly associated with the origin of the tumor. Intrahepatic and central cancers usually must be treated by liver surgery, whereas the majority of distal cholangiocarcinomas require pancreaticoduodenectomy. In case of a small, middle bile duct carcinoma, exclusive extrahepatic bile duct resection without pancreatic resection can be adequate. Five-year survival after radical resection is about 25%. Cancer of the distal bile duct has to be distinguished from ductal adenocarcinoma of the pancreas and carcinoma of the ampulla of Vater. Curative surgery is possible if the tumor is diagnosed early and radical resection is feasible. In this context, the role of an extended lymph node dissection remains unclear. To improve survival, future studies are needed to evaluate the role of novel adjuvant strategies (i.e., gemcitabine, capecitabine).