Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure which is seen in approximately 20% of all cases of acute pancreatitis and defines ‘severe acute pancreatitis’. Organ failure typically develops early in the course of acute pancreatitis, but may also develop later due to infected pancreatic necrosis induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome and therapy of organ failure in acute pancreatitis.