Infected necrosis in acute pancreatitis is one of the most dreaded complications of acute pancreatitis. Whereas selection of an appropriate antibiotic treatment of the infection poses no problem, prophylactic application of antibiotic remains controversial in the absence of symptoms of infection, but where contrast-enhanced CT scan clearly proves necrosis. This article discusses the present state of the art of the role of antibiotic prophylaxis in the treatment of acute pancreatitis and provides clinical guidelines.