Background and objectiveThe use of antibiotics in acute pancreatitis despite recent clinical trials remains controversial. The aim of this study is to review the latest clinical trials and guidelines about antibiotics in acute pancreatitis and determine its proper use.MethodsThrough a Medline search, we selected and analyzed pertinent randomized clinical trials and guidelines that evaluated the use of antibiotics in acute pancreatitis. We answered the most frequent questions about this topic.Results and conclusionBased on these clinical trials and guidelines, we conclude that the best treatment currently is the use of antibiotics in patients with severe acute pancreatitis with more than 30% of pancreatic necrosis. The best option for the treatment is Imipenem 3 × 500 mg/day i.v. for 14 days. Alternatively, Ciprofloxacin 2 × 400 mg/day i.v. associated with Metronidazole 3 × 500 mg for 14 days can also be considered as an option.