Abstract: Curative resection remains the most effective and the only potentially curative therapy for biliary tract cancer(BTC). Most of the patients with BTC present with an advanced (inoperable or metastatic) disease, and the relapse rate is high in those undergoing curative resection. In Meta-analysis, compared with surgery only, there was a significant improvement in overall survival with any adjuvant therapy after surgery. Although the BILCAP study failed to meet its primary endpoint by intention to treat analysis, a survival benefit was seen in a preplanned sensitivity analysis. Gemcitabine combined with cisplatin is still the first-line chemotherapy for patients with advanced disease. Gemcitabine with TS-1, or gemcitabine with cisplatin and TS-1 become an alternative to the first-line chemotherapy. IDH1 mutations and FGFR2 fusions have been positioned as the two main driving alterations in intrahepatic cholangiocarcinoma, and are the hot spots for targeted therapies. Immunotherapy alone or combined with other therapy is still on the way in the treatment of advanced BTC. This review discussed the past, present and exciting future of the medical treatments of cholangiocarcinoma.