A brief overview on the physiology and regulation of digestive enzyme secretion by the exocrine pancreas is presented. Knowledge about the physiology of the exocrine pancreas should help for a better understanding of the pathophysiology of both acute and chronic pancreatitis. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes, which leads to intracellular activation of trypsinogen, is still regarded as a key step in pathophysiology. The role of activation by cathepsins and the role of autoactivation of trypsinogen are still under debate. Studies on genetic alterations in various forms of human chronic pancreatitis can be interpreted that an imbalance between protease inhibitors and active proteases plays a key role. Toxic Ca2+ signals by excessive liberation from the endoplasmic reticulum may play another role. The mortality of necrotizing pancreatitis is still high. Early mortality is caused by a systemic inflammatory response syndrome with or without concomitant infection of necrosis; late mortality by multi-organ failure syndrome due to sepsis. Therapy of necroses should be performed as late as possible. A step-up approach using CT-guided and/or transgastric endoscopic necrosectomy seems to be superior to a primary surgical approach. A brief overview of the German S3 guidelines, not yet published, regarding diagnosis and treatment of chronic pancreatitis is presented.