The role of combined-modality therapy for pancreatic cancer is evolving with the recent development and completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive chemoradiotherapy or adjuvant chemoradiotherapy for local and/or regionally advanced disease. Our aim is to summarize the current state-of-the-art management and future directions regarding the multimodality approach to pancreatic cancer.