The survival of patients with pancreatic cancer is dismal: tumor's resection is possible in only 10-20% of patients. This has prompted clinical studies with chemotherapy and/or radiotherapy designed to increase the number of patients eligible for surgery, to maximize local tumor control and to improve the length of survival. Since postoperative chemoradiation is often delayed in these patients due to morbidity and prolonged recovery time associated with surgery, investigators are assessing the efficacy of chemoradiation before pancreatic resection in patients with potentially resectable pancreatic carcinoma or the potential to downstage locally advanced pancreatic cancer to resectable tumor. The analysis of several clinical trials published so far shows that results are conflicting and not definitive. No randomized clinical studies have been reported. Moreover, neoadjuvant therapy rarely leads to surgical downstaging allowing for potentially curative pancreatic resections. Novel multimodality approaches are required, and patients should be entered on clinical, controlled trials.