Biliary tract cancers (BTCs) include distal cholangiocarcinoma, perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma; these subtypes have distinct etiology, clinical presentation, and prognosis. Etiologies include embryologic, infectious, and inflammatory conditions, though most BTCs have no clear underlying cause. Treatment typically consists of upfront surgery for localized disease, which may include pancreatoduodenectomy, hepatectomy, cholecystectomy, or bile duct excision and reconstruction. Clinical trials of systemic therapy in these diseases typically include patients with all four types of BTC. Combination chemotherapy with immunotherapy is recommended in the first-line setting for advanced BTC. Targeted therapies have an increasing role in advanced BTC. Other therapies may be used in certain circumstances for advanced BTC, such as hepatic artery infusion pump for intrahepatic cholangiocarcinoma or liver transplant for perihilar cholangiocarcinoma.