Despite many prospective randomized clinical studies a specific pharmacotherapy for severe acute pancreatitis is not in sight. To date, the only possibility to influence the prognosis of this severe illness is early diagnosis and prevention of intra- and extrapancreatic necrosis and its subsequent infection. In severe necrotizing pancreatitis the incidence of infected necrosis amounts to 40–70% of all patients within 3 weeks. Thereby, the clinical picture often varies to large extent. Ultrasonographically or computertomography-guided fine-needle aspiration (FNAC) is a fast and reliable technique for diagnosis with an overall sensitivity of 88% and specificity of 90%. This method should however not be applied too early in the course of necrotizing pancreatitis. Since infection of pancreatic necrosis determines significantly the prognosis of disease, various studies have assessed the efficacy of prophylactic antibiotic treatment in patients. Three prospective randomized studies have shown that prophylaxis significantly minimizes septic complications, only in one study, however, the mortality rate could be improved. Although randomized studies are still mandatory to resolve the controversy, it seems justified to recommend prophylaxis with antibiotics which are capable of penetrating the pancreatic tissue and juice. Sterile necrosis should be treated conservatively, with prophylactic antibiotic treatment for as long as possible. Only if patients worsen despite intensive care medicine, surgical debridement should be considered. In contrast, in patients with infected necrosis immediate surgery is in most cases mandatory. Although in one prospective study conservative treatment did not lead to an enhanced mortality rate, possible delay of surgical treatment may endanger the patient. In order to improve the prognosis of the disease, timely and adequate treatment in specialized units provides the best chances for a good prognosis whereby the severely ill patient should not be treated according to a scheme but to his/her individual needs.