Pancreatoduodenectomy should be considered only in those patients whose tumors appear to be resectable based on high-quality CT and who have a good performance status. Furthermore, pancreatoduodenectomy should be part of a multimodality treatment program that includes preoperative or postoperative chemoradiation. Because of the modest survival rates associated with current treatments, the enrollment of all patients into clinical trials of new combinations of surgery, chemoradiation, and newly developed systemic drugs is strongly encouraged. Future progress in the treatment of pancreatic cancer will involve techniques for early diagnosis and effective systemic therapy. For now, the best results can be achieved by careful attention to patient selection, preoperative assessment of resectability, surgical technique, and postoperative care.