The medical management of acute pancreatitis is primarily supportive and involves making the patient nulla per os, providing adequate intravenous hydration, and controlling pain with analgesics. Systems to identify patients with severe pancreatitis at risk for morbidity and mortality are available but require supplementation with frequent, experienced clinical observation. A number of modalities to inhibit pancreatic secretion or pancreatic proteases have not been successful in clinical trials, although larger studies in patients with more severe pancreatitis are required to ultimately assess their effectiveness. The empiric use of imipenem and long-term peritoneal lavage in patients with severe or necrotizing pancreatitis appear promising but further studies are needed. The removal of impacted gallstones in patients with severe pancreatitis or cholangitis is useful, provided an expert endoscopist is available. Improvements in our ability to document pancreatic infection early by CT-directed aspiration have markedly improved our ability to manage pancreatic infection.