The term localized disease as it applies to pancreatic adenocarcinoma encompasses distinct entities associated with varied prognoses and therapeutic recommendations. These include three disease categories: (1) disease that is localized and resectable, (2) localized disease that is borderline resectable, and (3) unequivocally unresectable pancreatic adenocarcinoma, all representing a continuum. The incorporation of systemic chemotherapy into the management of pancreatic adenocarcinoma at all stages has become standard of care, and the basis for this is discussed with reference to the major clinical trial landmarks. The role of radiation therapy (in association with concomitant chemotherapy) in the management of localized pancreatic adenocarcinoma, however, has become less clear and represents an area of management confusion in this disease. Going forward, with the expectation of new and improved systemic agents, locoregional tumor control and, hence, chemoradiotherapy are anticipated to have a greater role and impact.