In intensive care medicine, severe acute pancreatitis (SAP) remains a very challenging disease with multiple complications and high mortality. The main pathophysiological mechanisms determining outcome are an uncontrolled systemic hyperinflammatory response early on and infection of pancreatic necrosis later on in the disease process. Despite a better understanding in recent years of the mechanisms and the mediators involved in the hyperinflammatory response, there is, as yet, no generally recognized specific treatment for this disease. Since early identification and aggressive treatment of associated organ dysfunction can have a major impact on outcome, early assessment of prognosis and severity is important. The evidence available indicates that patients with severe acute pancreatitis do not benefit from therapy with available antisecretory drugs or protease inhibitors. Supportive therapy, such as vigorous hydration, analgesia, correction of electrolyte and glycemia disorders, and pharmacological or mechanical support targeted at specific organs, is still the mainstay of therapy. In spite of meager evidence, prophylactic antibiotics with good penetration in pancreatic tissue are recommended in severe acute pancreatitis. Enteral nutrition via a nasojejunal tube has become the preferred route of feeding. Most patients with sterile necrosis do not benefit from surgical intervention. In patients with proven infection of pancreatic tissue, surgery is necessary. Percutaneous, radiological drainage techniques may eventually become an alternative form of drainage in selected patients.