Abstract: In most cases, acute pancreatitis is a self-limited condition that improves with supportive treatment. In 15% to 20%, severe acute pancreatitis develops, characterized by necrosis, multiorgan failure, infection, and other complications. There is an early and a late peak of severity in the natural course of acute pancreatitis. Pancreatic infections occur in 3 settings: free fluid collections, pseudocysts, and necrosis. The main mechanism of infection is translocation of microbes from the gut. Infection may be suggested by gas bubbles within pancreatic tissue or fluid collections seen with computed tomography or magnetic resonance imaging, as well as laboratory markers such as procalcitonin and IL-8. However, accurate diagnosis and confirmation requires guided needle aspiration of the infected fluid or tissue. Use of prophylactic antibiotics does not confer any mortality benefit. Infected fluid collections are generally treated with percutaneous or endoscopic drainage. Infected necrosis usually requires surgical intervention, but this should be delayed for at least 2 weeks after the onset of acute pancreatitis, allowing for better demarcation of the necrotic tissue from the viable pancreatic parenchyma. In select cases of infected necrosis, there may be a role for conservative treatment, but this needs to be further studied.