Approximately 150,000 people worldwide and 40,000 people in Europe die each year of pancreatic cancer,making it one of the five leading causes of cancer-related death and one of the most aggressive human tumors. Resection is still the only option that offers a chance of cure for pancreatic cancer patients. Recent studies have highlighted the correlation between the number of pancreatic resections per year and postoperative mortality. Thus, large centers of pancreatic surgery have mortality rates below 5%, whereas centers with lower caseloads have mortality rates exceeding 10%. Standards have been established for the surgical treatment of pancreatic cancer;however, these are often not based on evidence derived from randomized, controlled studies. Resection for pancreatic cancer is carried out if there are no metastases present and if the tumor is locally resectable; i.e., if there is no complex vessel invasion. However, an isolated infiltration of the portal vein is not considered a contraindication for surgery. At present, there are no evidenced-based data available on palliative (R2) resections,which might be a therapeutic option in centers with low morbidity/mortality. Three randomized controlled trials clearly show that the pylorus-preserving Whipple is equal to the classical Whipple in terms of oncological effectiveness, morbidity, and quality of life. Therefore, the pylorus-preserving Whipple is increasingly considered the standard operation for tumors of the pancreatic head. Based on randomized trials, extended lymph node dissection cannot generally be recommended for pancreatic cancer. Further prospective, randomized, multicenter trials have to be carried out in the upcoming years to find new approaches in the therapy of pancreatic cancer and to establish evidence-based treatment strategies for this disease.