Biliary tract cancer, or cholangiocarcinoma, arises from the biliary epithelium of the small ducts in the periphery of the liver (intrahepatic) and the main ducts of the hilum (extrahepatic), extending into the gallbladder. The incidence and epidemiology of biliary tract cancer are fluid and complex. It is shown that intrahepatic cholangiocarcinoma is on the rise in the Western world, and gallbladder cancer is on the decline. Radiation therapy has emerged as an important component of adjuvant therapy for resected disease and definitive therapy for locally advanced disease. The emerging sophisticated techniques of imaging tumors and conformal dose delivery are expanding the indications for radiotherapy in the management of bile duct tumors. As we understand more about the molecular pathways driving biliary tract cancers, targeted therapies are at the forefront of new therapeutic combinations. Understanding the gene expression profile and mutational burden in biliary tract cancer allows us to better discern the pathogenesis and identify promising new developmental therapeutic targets.