Because of advanced molecular physiology techniques, there is new information about how fever affects the body. Now, fever is identified as a cascade of physiologic events, not just a single symptom. This article, the first in a set of two on the physiology of fever, focuses on the role of cytokines as the trigger for the physiologic cascade of fever. (Watch for Part 2 in the next issue of DCCN, which challenges the assumption that cooling interventions are appropriate for all febrile patients.