The treatment of severe acute pancreatitis remains largely supportive because pharmacotherapy that affects the clinical course has yet to be realized. The consequences of severe acute pancreatitis that contributes to increase morbidity and mortality include systemic inflammatory response syndrome and pancreatic necrosis. Tumor necrosis factor-alpha (TNF-α) is felt to be a major mediator of these adverse outcomes. In this issue of Gastroenterology, Vege et al report on their results of a double-blind, placebo-controlled, randomized trial that test the efficacy of pentoxifylline, a xanthine derivative that inhibits phosphodiesterase and the effects of TNF-α.