Postoperative pancreatic fistula (POPF) is the most common and also the most threatening complication following distal pancreatectomy. For this reason, morbidity and mortality of this operation remain still high. Over the last two decades, many different studies have been performed aiming to reduce the rate and the severity of POPF. However, effective treatments to prevent or avoid clinically relevant pancreatic fistula are still unclear. In this review, we discuss the current evidence on such a relevant topic.