The role of multimodality therapy and surgery for the treatment of locally advanced pancreatic cancer remains to be determined. Although no randomized trials have been done to determine the optimal management of this difficult clinical problem, numerous series reporting successful surgical resection with negative (R0) or microscopic margin (R1) showing favorable long-term survival provide a basis for an aggressive approach in selected cases of advanced cancer of the pancreas. In the absence of conclusive clinical trials, neoadjuvant treatment followed by surgical resection seems to be the optimal approach for locally advanced pancreatic cancers when the potential for surgical resection is suggested by preoperative high quality CT imaging. In particular, when the tumor is within the criteria for borderline resectable pancreatic cancer, efforts to achieve R0 resection are warranted. For those selected cases invading the hepatic artery and superior mesenteric artery, combined arterial resection and reconstruction may be performed to achieve R0 resection. Nonetheless, such a complex procedure should be balanced by a high rate of postoperative complications. In contrast, in cases of tumors invading the celiac axis, R0 resection by combined celiac axis resection can be performed without a high rate of postoperative complications. Survival benefit needs to be verified by further studies in the future.