Cholangiocarcinoma is an epithelial cell malignancy arising from varying locations within the biliary tree showing markers of cholangiocyte differentiation. The most contemporary classification based on anatomical location includes intrahepatic, perihilar, and distal cholangiocarcinoma. Intrahepatic cholangiocarcinoma is defined as a cholangiocarcinoma located proximally to the second degree bile ducts (proximal and distal refers to the direction of bile flow such that the intrahepatic bile ducts are proximal to the common bile duct); within the liver, perihilar cholangiocarcinoma is localised to the area between the second degree bile ducts and the insertion of the cystic duct into the common bile duct; whereas distal cholangiocarcinoma is confined to the area between the origin of the cystic duct and ampulla of Vater.1 Most cholangiocarcinomas are well, moderately, and poorly differentiated adenocarcinomas with other histological subtypes encountered rarely.2,3 Surgical treatment is the preferred option for all subtypes, but, when contemplated, involvement of the vascular structures and lymph nodes needs to be considered. The highly desmoplastic nature of cholangiocarcinoma, its extensive support by a rich tumour microenvironment, and profound genetic heterogeneity, all contribute to its therapeutic resistance. Although surgery and curative liver transplantation are options for selected patients with perihilar cholangiocarcinoma, 5-year survival rates are very low. The chemotherapy regimen of gemcitabine and cisplatin is often used for inoperable disease. Locoregional therapies are used for intrahepatic cholangiocarcinoma, but conclusive evidence for efficacy is lacking. Understanding of cholangiocarcinoma biology, the oncogenic landscape of this disease, and its complex interaction with the tumour microenvironment could lead to optimum therapies with improvement in patient survival. In view of much recent interest in this disease, a review of recent medical advances for cholangiocarcinoma is both timely and topical. In this Seminar we focus mainly on intrahepatic and perihilar cholangiocarcinoma because progress has predominantly occurred in these subtypes (panel).