Necrotizing pancreatitis continues to challenge clinicians, and few other medical subjects currently elicit as much debate. Host characteristics or underlying differences in pathophysiology that lead to pancreatic necrosis remain poorly understood. Severe pancreatitis follows a two-phase clinical course. The early first phase manifests the features of the systemic inflammatory response syndrome, and the second late phase is characterized by infectious complications. This article presents a multidisciplinary literature-based approach to the treatment of patients with necrotizing pancreatitis.