Fever is common among patients admitted to intensive care units (ICUs). In spite of the frequency of its occurrence, the biological mechanisms regulating the initiation and progression of fever are poorly understood. In addition, there are few large studies reporting on the epidemiology and etiology of fever in general medical and surgical ICU patients. Current evidence suggests that the development of high fever by patients admitted to ICUs with a medical admission diagnosis is associated with an increased risk of death. The decision to treat fever should therefore be obvious, but several lines of evidence argue against temperature-lowering strategies. Furthermore, the use of different temperature control strategies in febrile patients without acute brain injury or acute myocardial infarction is guided by a paucity of randomized clinical trials and by a lack of understanding of the biology of the induction and control of fever. As such, a review of the epidemiology, molecular mechanisms, and immunology of fever as well as the evidence behind management of fever in the critically ill is pertinent to all critical care practitioners.