Pancreatic adenocarcinoma is one of the most lethal malignancies, with an overall 5-yr disease-free survival rate of 1–2% for all patients. Most patients with pancreatic cancer are not diagnosed until they have developed locally advanced or regionally disseminated disease that is not amenable to attempted curative surgical resection. Chemotherapy and radiation therapy have only modest benefit in this stage of the disease and typical survival is 6 mo. Among those patients with apparently resectable disease who undergo surgical exploration, between 20 and 40% are found to be unresectable, dependent on the pre-operative evaluation. Even those pancreatic cancer patients who have a margin-negative resection have a 5-yr disease-free survival of less than 30%, and approximately half of patients surviving 5 yr will relapse between 6 and 10 yr. Thus, the treatment of pancreatic cancer remains a significant challenge to the surgical, radiation, and medical oncologist.