In single-institution studies, IORT at appropriate doses seems to safely improve local control in patients who have locally advanced pancreatic cancer, compared with historical controls. IORT also has been a component of adjuvant treatment programs that have led to excellent local control in resected patients. When considering the use of IORT, it is essential to have an understanding of the physical characteristics of the electron beam and how it can differ with the use of flat and beveled applicators. Although apparent improvement in local control with the use of IORT seems to have produced some improvement in median survival rates, high rates of distant failure continues to prevent a significant improvement in long-term survival. Because effective local control in patients with unresectable pancreatic cancer is a prerequisite to the development of curative therapies, the development of improved systemic therapies in patients with locally advanced pancreatic cancer will likely make local therapies such as the use of IORT even more important in the future.