For decades, sepsis research has been motivated by the idea of a dangerous overreaction of the immune system in sepsis. But is it true that the response to sepsis is dysregulated? This review surveys the history of sepsis trials and found that evidence for dysregulation does not exist in many of the physiologic mechanisms of sepsis. It is time to consider the alternative hypothesis, that sepsis traits are often functional, and do more harm than good. This review discusses the implications of this perspective for the future of sepsis research