Infected pancreatic necrosis (IPN) is one of the main causes of mortality in patients with acute pancreatitis (AP). The choice of antibiotic therapy in AP should be based on penetration of the drug in the pancreas and the degree of coverage provided against the typical bacterial flora produced in IPN. Drugs such as imipenem, ciprofloxacin and metronidazole have been widely studied and seem to be ideal in the treatment of INP. Clinical practice guidelines recommend a carbapenem agent as the initial empirical treatment. When Gram-positive pathogens are isolated in pancreatic samples, vancomycin can be used alone or associated with a carbapenem. Currently, prophylactic antibiotic therapy for IPN is not supported by the scientific evidence, since both the best quality studies (double-blind) and the latest meta-analysis published have found no benefit of the use of this strategy.