Fever is a very common sign to observe in critically ill children during their Intensive Care Unit stay, which should be understood as an evolutionary biological response of normal adaptive character from the host to physiological stress. It is the result of a complex response to pyrogenic stimuli, resulting in the generation of cytokines and prostaglandins. The molecular mechanisms involved in the onset of fever are not yet fully specified. Therefore, difficulties in the knowledge of the exact pathophysiological processes involved are created, so it is necessary to elaborate an adequate and specific therapeutic strategy. Experimental studies conclude that fever and inflammation are beneficial to the host. However, antipyretic therapy is commonly employed, and human studies on the presence of fever and its treatment for the prognosis of critically ill septic patients are inconclusive. Up-to-date information on the physiology of human thermoregulation, the effect of temperature on the febrile range over multiple biological processes involved in host defense, and thermoregulatory interventions in the septic patient are essential to know by the critical care physician.