Cholangiocarcinoma (CCA) is a malignant tumor originating from the biliary system. Although surgery is the recognized radical treatment for CCA, the treatment results are not satisfactory due to the special anatomical characteristics of the biliary system and the high aggressiveness of the disease. Drug therapy has become an option for patients with advanced CCA to achieve a better outcome. Drug treatment mainly includes chemotherapy, targeted therapy and immunotherapy. At present, two important therapeutic targets, the fibroblast growth factor receptor and isocitrate dehydrogenase 1, have been found in studies, and the targeted therapeutic drugs against them generally showed positive effects in clinical trials. Although CCA generally expresses PD-1/PD-L1, it is not sensitive to immune checkpoint inhibitors, and the efficacy can be improved by combining other immunotherapy drugs. Traditional chemotherapy has the most stable efficacy for CCA compared with emerging targeted therapies and immunotherapies. The National Comprehensive Cancer Network guidelines recommend cisplatin plus gemcitabine as the first-line chemotherapy regimen for patients with advanced unresectable CCA or CCA presenting with metastatic symptoms. Recent advances in these drugs will significantly improve the survival benefits of CCA patients.