Regardless of whether the initiating event is alcohol, gallstones or some other less common cause, acute pancreatitis progresses in a predictable manner eventually leading to failure of multiple unrelated organs. Very quickly following the inciting event, a local inflammatory process is initiated which results in the local production of inflammatory mediators. Virtually all patients with acute pancreatitis will experience some symptoms related to this local inflammation, with some resolving completely at this point. Most patients will go on to develop a systemic hyperinflammatory state expressed as the development of fever, tachycardia, tachypnea, and mild acid-base disturbances. Although this systemic hyperinflammatory state is usually mild, occasionally it may be very severe resulting in overt distant organ failure. With a more thorough understanding of the inflammatory mediators responsible for this hyperinflammatory state, many new therapeutic approaches are on the horizon.