BACKGROUND: Cholangiocarcinoma (CC) is the second most common primary malignant liver disease. During the last decades, various novel therapies have been introduced in the field of oncology; nevertheless, the number of treatment options for CC is still limited. METHODS: In this article, current palliative chemotherapy concepts as well as new drug therapies are outlined. RESULTS: Gemcitabine and cisplatin are the standard treatment of care for patients with inoperable CC. Second-line chemotherapy is not standardized yet and is dependent on the first-line compounds. Antibodies against VEGFR and EGFR showed mixed or negative results. New molecular systemic treatments are not established yet. CONCLUSION: Many clinical trials are still ongoing and new therapeutic strategies, including immunotherapies, are under active investigation.