Malignancies of the biliary tract are rare, diagnosed in approximately 9,000 patients each year in the United States (1). Unfortunately, most patients present with advanced disease. Of the small subset who present with resectable (and thus potentially curable) disease, many experience recurrence (2), reinforcing the fact that a multidisciplinary approach to these cancers is critical. Traditionally, our success with medical therapy for patients with locally advanced or metastatic disease has been poor. Recently, however, the ABC-02 trial demonstrated a survival advantage with the combination of gemcitabine and cisplatin as compared to gemcitabine monotherapy (11.7 vs. 8.1 months, P<0.0001) and established the combination regimen as standard-of-care for advanced biliary tract cancers (3). Although this trial does provide a step in the right direction, we must maintain a healthy sense of humility and accept the fact that the molecular complexity of these tumors will not be overcome with one or two drugs. As our knowledge and understanding of the molecular basis of cancer slowly improves, interest in the development and clinical application of molecular targeted therapy (MTT) is increasing.