Shock states are characterized by a pronounced activation of numerous cell types that lead to an acute inflammatory reaction. The exact mechanism by which these inflammatory cells are activated is not known. Numerous studies have implicated the gastrointestinal tract as one of the main sites for the generation of inflammatory mediators and initiation of an acute systemic response. The pancreas is known to secrete powerful digestive enzymes, and we hypothesize that they may play a leading role in the pathogenesis of multiorgan failure after the onset of shock. We carried out a search in PubMed for all relevant studies related to the role of the pancreas in shock. Studies that included information concerning the role of pancreatic enzymes in shock were then summarized. Our article serves to review the current hypotheses on how digestive enzymes produced by the pancreas may play a pivotal role in initiating the systemic inflammatory response. We further hypothesize how these enzymes and/or their products may ultimately contribute to multiorgan failure and death.