Cholangiocarcinoma is a rare malignancy associated with poor prognosis and high mortality. Surgical resection is the only chance for cure depending on careful patient selection. There are no well-conducted studies regarding the role of adjuvant chemotherapy. Preliminary data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy. The literature regarding treatment results with specific regimens in the adjuvant setting is limited and no general recommendation can be given. In patients with locally advanced or metastatic disease, most studies are small, non-randomized phase II trials, and many studies comprise a mix of bile duct cancers, gallbladder cancer, and either pancreatic or hepatocellular cancers. In metastatic cancer, phase II studies with several cytotoxics, including gemcitabine, the platinums, and the fluoropyrimidines, have shown a modest and often short-lasting activity. No single chemotherapy agent or combination regimen can therefore be recommended as a standard of care at present. In this review, we give an overview of chemotherapy in the adjuvant, neoadjuvant, and advanced settings.