Infectious complications are the leading cause of death in patients with severe acute pancreatitis. Currently, there is controversy concerning the therapeutic possibilities to reduce the incidence of bacterial infection in this disease. Numerous studies are available which apparently support the prophylactic use of antibiotics in patients with necrotizing pancreatitis. The results, however, are contradicting and interpretation is difficult as these studies have used various antibiotic drugs with different application schemes and heterogeneous study end points. This article gives a critical overview of the background of antibiotic treatment in severe acute pancreatitis, the published data on antibiotic treatment and an outlook on the topics that need to be addressed by future research.