Biliary Tract Cancer is a rare and aggressive tumor characterized by unresponsiveness to chemotherapy and radiotherapy in the vast majority of cases. Surgery offers the only possibility of a cure, though post-operative disease recurrence is common. Only few randomized trials with few patients have been conducted to in this setting of patients and standard chemotherapy has not been established yet.This article summarizes the most important clinical trials regarding chemotherapy for biliary tract cancer and the first evidences regarding the adjuvant treatment. Moreover the clinical trials evaluating targeted therapy will be described, especially those assessing the role of anti-EGFR and antiangiogenic agents.