Postoperative pancreatic fistula (POPF) is the most common major complication after pancreatoduodenectomy (PD) and it can lead to prolonged hospital stay, increased costs, and mortality. The POPF rate is strictly correlated to the definition applied, but there are so many different definitions in the literature that comparison between published series of patients is difficult. The International Study Group of Pancreatic Fistula (IGSPF) has developed a new definition, with a grading system able to stratify complicated patients into three groups, based upon the clinical implications and costs of their postoperative course. The most important risk factors identified are a soft pancreatic texture and a main pancreatic duct diameter of 3 mm or less. Several surgical techniques have been studied in order to prevent anastomotic leakage, but none has been demonstrated to be superior to others. The use of somatostatin analogues is still matter of controversy. Conservative management of POPF is usually effective, but in patients with deteriorating clinical status with evidence of sepsis, surgical management is needed.