Neoadjuvant chemoradiation has demonstrated significant advantages in the management of pancreatic adenocarcinoma. A similar tumor in a nearby anatomical location is extrahepatic cholangiocarcinoma, which has proven to be largely unresponsive to current forms of therapy. Neoadjuvant therapy for hilar cholangiocarcinoma has been combined with surgical resection and/or liver transplantation with a 25-33 % complete pathological response rate. We propose a wider application of neoadjuvant chemoradiation for patients with distal cholangiocarcinoma and present our rationale for this form of treatment sequencing.