The diagnosis of acute pancreatitis requires two of the following three features: 1) characteristic abdominal pain, 2) serum amylase and/or lipase ≥3 times the upper limit of normal, and 3) characteristic findings of acute pancreatitis on CT scan. Risk factors of severity of acute pancreatitis at admission include older age, obesity, and organ failure. Tests at admission that are also helpful in distinguishing mild from severe acute pancreatitis include APACHE-II score ≥8 and serum hematocrit (a value <44 strongly suggests mild acute pancreatitis). An APACHE-II score that continues to increase for the first 48 h strongly suggests the development of severe acute pancreatitis. A CRP >150 mg/L within the first 72 h strongly correlates with the presence of pancreatic necrosis. The two most important markers of severity in acute pancreatitis are organ failure (particularly multisystem organ failure) and pancreatic necrosis. Contrast-enhanced CT scan is the best available test to distinguish interstitial from necrotizing pancreatitis, particularly after 2-3 days of illness. Mortality of sustained multisystem organ failure in association with necrotizing pancreatitis is generally >36%. Supportive care includes vigorous fluid resuscitation that can be monitored in a variety of ways including a progressive decrease in serum hematocrit at 12 and 24 h. Supplemental oxygen should be administered during the first 24-48 h, bedside oxygen saturation monitored at frequent intervals, and blood gases obtained when clinically indicated, particularly when oxygen saturation is ≤95%. Transfer to an intensive care unit is recommended if there is sustained organ failure or if there are other indications that the pancreatitis is severe including oliguria, persistent tachycardia, and labored respiration. Patients who are unlikely to resume oral nutrition within 5 days because of sustained organ failure or other indications require nutritional support. Nutiritional support can be provided by TPN or by enteral feeding. There appear to be some advantages to enteral feeding. Patients with acute pancreatitis caused by gallstones, who are strongly suspected of harboring common bile duct stones on the basis of organ failure or other signs of severe systemic toxicity (marked leukocytosis and/or fever), require evaluation for the presence of choledocholithiasis, preferably within the first 24 h of admission. ERCP with endosocopic biliary sphincterotomy and stone removal are indicated for patients with cholangitis, severe acute pancreatitis, or high clinical suspicion or definitive demonstration of persistent bile duct stones by other imaging techniques. Expectant management with interval cholecystectomy including intraoperative cholangiogram is appropriate for most patients with mild to moderate pancreatitis and an improving clinical course. Routine precholecystectomy ERCP is not recommended in patients with biliary pancreatitis. In ambiguous cases, where available, evaluation for bile duct stones can beperformed by endoscopic ultrasound or MRCP. The use of prophylactic antibiotics in necrotizing pancreatitis is not recommended in view of a recent prospective randomized double-blind trial that showed no benefit and in view of the concern that the prolonged use of potent antibiotic agents may lead to the emergence of resistant Gram-positive organisms and fungal infections in the necrotic pancreas. It is reasonable to administer appropriate antibiotics in necrotizing pancreatitis associated with fever, leukocytosis, and/or organ failure while appropriate cultures (including culture of CT-guided percutaneous aspiration of the pancreas) are obtained. Antibiotics should then be discontinued if no source of infection is found. CT-guided percutaneous aspiration with Gram's stain and culture is recommended when infected pancreatic necrosis is suspected. Treatment of choice of infected necrosis is surgical debridement. The timing of surgery is left to the discretion of the pancreatic surgeon. Patients who are medically unfit for open surgical debridement can be treated with less invasive surgical techniques, radiologic techniques, and, at times, endoscopic techniques in medical centers with these capabilities. Treatment of sterile pancreatic necrosis is generally medical during the first several weeks even in the presence of multisystem organ failure. Eventually, after the acute inflammatory process has subsided and coalesced into an encapsulated structure that is frequently called organized necrosis, debridement may be required for intractable abdominal pain, intractable nausea or vomiting caused by extrinsic compression of stomach or duodenum, or systemic toxicity (fever and/or intractable malaise). Debridement can be performed by surgical, endoscopic, or radiologic techniques.