Physicians have used various forms of antipyretic therapy since antiquity to lower the temperature of febrile patients. Nevertheless, it has yet to be determined whether the benefits of antipyretic therapy outweigh its risks. It is not known, for example, if core temperatures encountered during the febrile state ever reach levels that are intrinsically noxious (and therefore merit antipyretic intervention) or when, if ever, fever's metabolic costs exceed its physiologic benefits, or if the benefits of symptomatic relief afforded by antipyretic drugs consistently exceed their toxicologic cost. Whereas preliminary experimental and clinical observations suggest that antipyretic therapy has the potential to increase the duration and/or severity of certain infections, such data are as yet too fragmentary to draw firm conclusions regarding their validity. Finally, although clinicians have long suspected that bacteremia and other severe infections might induce fevers that are less responsive to antipyretic therapy than are those associated with self-limited infections, this concept has not held up under scientific scrutiny. Thus, despite over 2.5 millennia of clinical experience, important questions regarding the risks and benefits of antipyretic therapy remain to be answered.