CONCLUSIONS Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. BACKGROUND The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. RESULTS Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. CONCLUSIONS Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.