Since several decades, the role of surgery in PDAC patients has been crucial. Historically, the indications for surgical resection have been based mostly on anatomical factors. Almost all the classification existing on PDAC resectability are based on the involvement of peri-pancreatic blood vessels. Even if this approach has been always debated, recently some revolutionary improvement in PDAC treatment made these definitions less reliable. With the introduction, approximately a decade ago, in clinical practice, of new multi-agent chemotherapies, some of the dogma in pancreatic cancer treatment are falling. In the recent years we learned that radiology cannot “stage” properly pancreatic cancer after neo-adjuvant treatment. Only 20-25% of patient receiving neo-adjuvant treatment have a radiological response, even if, the clinical response is much higher. Other data suggested that the long-term survival of patient who underwent resection after neo-adjuvant therapy is similar in primary resectable, border-line resectable and locally advanced pancreatic cancer. All these information contributed to a paradigm shift in pancreas cancer treatment. In the modern era of pancreatic surgery, biology should dominate anatomy in defining the indications for surgery. As a direct consequence of this new idea, more advanced operations, sometimes involve complex vascular resections and reconstructions, could be beneficial in patient who respond well to chemotherapy and with a more favorable biology. Still many open questions remain. How can we better select patients, how can we measure the response to chemotherapy, where these operations can be safely performed? In the coming years, with the further improvement of chemotherapies, surgery will gain probably an even more important role in the multimodal treatment of pancreatic cancer, therefore a dedicated training to perform complex procedures will become a crucial step for the next generation of pancreatic surgeons.