Infectious complications currently account for 80 percent of deaths from acute pancreatitis. The adjunctive role of antibiotics in the prevention and treatment of secondary pancreatic infections has received insufficient attention. Randomized clinical studies of effective antibiotics for prophylaxis or empiric therapy of pancreatic infections do not currently exist. In their absence, it is not known whether prophylactic antibiotics are useful in patients with acute pancreatitis. Until such studies are available, if antibiotics are to be used, their choice must be based upon indirect criteria: the ability of the antibiotic to effectively penetrate pancreatic tissue and juice, knowledge of the most common pancreatic pathogens, and the ability of the antibiotic to exceed the in vitro concentration (MIC-90) in pancreatic juice for the common pathogens. Recognition of the limited state of knowledge regarding antibiotics in acute pancreatitis may stimulate future investigations.