Cholangiocarcinoma presents a formidable diagnostic and treatment challenge. The majority of patients present with unresectable disease and have a survival of less than 12 months following diagnosis. Progress has been made by the appropriate selection of patients for treatment options including resection, with the routine use of more aggressive resections in order to achieve margin-negative resections. This has resulted in longer survival times for these patients. Neoadjuvant and adjuvant therapies have, for the most part, not improved survival in patients with this tumor, and new strategies are needed to improve this line of therapy. The prognosis for unresectable patients is poor, and palliative measures should be aimed at increasing quality of life first and increasing survival second.