Severe acute pancreatitis (SAP) is characterized by an unregulated systemic proinflammatory response secondary to activation of trypsin within the pancreatic tissue, resulting in multiple organ failure. This dysregulated inflammation leading to organ dysfunction also characterizes severe sepsis. Activated protein C (APC) has pleotropic effects on the immune, coagulation, inflammatory and apoptotic pathways, and has been postulated to benefit acute pancreatitis--although concerns of possible retroperitoneal bleeding remain. Currently, experimental studies and subgroup data on patients with pancreatitis from a randomized controlled trial of APC in severe sepsis form the literature on the possible role of APC in SAP. We review the first randomized controlled trial of APC in acute pancreatitis published in the present issue of Critical Care.