The role of radiation therapy in the management of locally advanced pancreatic cancer is controversial. Despite its localized presentation, locally advanced pancreatic cancer is characterized by high rates of metastases. Historic data have been mixed, and newer studies have called into question the use of radiation therapy. However, it appears that patients more likely to benefit from chemoradiation can be identified with an induction phase of chemotherapy. Data evaluating this approach suggest that approximately 30% of patients will develop metastatic disease within the first 3 to 4 months of chemotherapy. Patients without progression who receive chemoradiation therapy may experience improved survival. Future directions include the validation of this strategy and the integration of biologic agents.