Pancreatic cancer is the fourth leading cause of cancer deaths in the USA. Although some patients will present with premalignant pancreatic lesions (i.e., intraductal papillary mucinous neoplasms) or localized tumors amenable to curative resection, the majority of patients will unfortunately present with technically unresectable or metastatic disease. This review of the recent medical literature will discuss the optimal work-up and management of premalignant pancreatic lesions and the surgical management of localized, borderline resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will focus on new criteria used to define surgical "resectability," the significance and clinical impact of surgical margins, the role of multimodality therapy in the management of patients with borderline resectable or locally advanced tumors, the role of surgery for local or distant recurrence, and minimally invasive surgical approaches.