In this paper, selected historical aspects of thermoregulation and fever are presented as background to the application of molecular biology to thermoregulation. Temperature-sensing mechanisms, coordination of thermal information, thermoregulatory circuitry, efferent responses to thermal stimuli, set point mechanisms, and some of the mechanisms and consequences of fever and hyperthermia are highlighted. Neurotransmitters used in thermoregulatory circuits are also discussed. An attempt is made to include information from comparative physiological sources. Possible future avenues of research in the light of recent new technologies are also presented.