The clinical course of an episode of acute pancreatitis varies from a mild, transitory illness to a severe often necrotizing form with distant organ failure and a mortality rate of 20-40%. Patients with severe pancreatitis, representing about 15-20% of all patients with acute pancreatitis, need to be identified as early as possible after onset of symptoms allowing starting intensive care treatment early in the disease process. An episode of severe acute pancreatitis progresses in two phases. The first 10-14 days are characterized by a systemic inflammatory response syndrome maintained by the release of various inflammatory mediators. The second phase, beginning about 10-14 days after the onset of the disease is dominated by sepsis-related morbidity due to infected peripancreatic and pancreatic necrosis. This state is associated with septic multiple organ systemic failure. The importance of infection on the outcome of necrotizing pancreatitis has been clearly delineated and the pre-emptive use of broad-spectrum antibiotics that achieve effective tissue concentrations is considered standard management of patients with severe necrotizing pancreatitis, especially if associated with organ failure or extended necrosis. Patients with infected necrosis should undergo a surgical intervention. The standard open technique consisting of an organ preserving necrosectomy followed by a postoperative concept of lavage and/or drainage to evacuate necrotic debris occurring during the further course has recently been challenged by various minimally invasive approaches.