Since antiquity, physicians have beheld infections with deep consternation, knowing that a local lesion can have horrific systemic effects. Even in modern times, these effects have generally been impossible to control. Until recently, their ultimate cause was not well understood. Now, within the space of only a few years, the proximal cause of sepsis has been identified. Paralogous members of the Toll-like receptor (TLR) family sense infection and ignite the systemic inflammatory reaction that is known as sepsis. The question at hand has become a practical one: can this understanding be exploited to a therapeutic advantage?