Sepsis—a complication of infection—is a factor in at least a third of all hospital deaths—a sobering statistic . Patients with sepsis frequently present with fever, shock, and multiorgan failure. Because of this dramatic clinical scenario, investigators have generally assumed that sepsis mortality is due to unbridled inflammation . Research in animal models, in which administration of the cytokines tumor necrosis factor–α (TNF-α) and interleukin-1 (IL-1) reproduced many features of sepsis, supported that assertion. Yet, over 40 clinical trials of agents that block cytokines, pathogen recognition, or inflammation-signaling pathways have universally failed (, ). However, on page 1260 of this issue, Weber et al. show that blocking a cytokine—specifically, IL-3—can indeed be protective against sepsis.