Cholangiocarcinoma is a relatively uncommon malignancy, that presents late in the vast majority of cases. Overall survival rates are extremely poor and treatment options remain limited in patients with inoperable, recurrent or metastatic disease. Systemic chemotherapy has historically had little impact on the natural history of this disease, owing to both the absence of agents with substantial activity and the overall morbidity of treatment in this patient population. Response rates with 5-fluorouracil have been 10% at best, with a median survival of 6 months. However, there has been interest in the use of newer cytotoxic drugs and combination regimens in advanced cholangiocarcinoma, and Phase II trials have reported much improved results. This review examines this data and assesses whether a new standard of care for advanced cholangiocarcinoma can be found.