Of the 32,180 patients diagnosed with pancreatic carcinoma in the United States this year, approximately 40% will present with locally advanced disease. Radiotherapeutic approaches are often employed because these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases. These treatments include external-beam irradiation with and without fluorouracil-based chemotherapy, intraoperative irradiation, and, more recently, external-beam irradiation with new systemic targeted agents.