Despite minor daily and monthly cyclical variations, body temperature remains relatively constant. Core temperature is maintained by thermoregulatory responses such as sweating, vasoconstriction and shivering, which are largely controlled by the hypothalamus. Within the hierarchy of neural structures regulating autonomic thermoregulatory responses, the preoptic area of the anterior hypothalamus plays a dominant role. In contrast, the posterior hypothalamus mediates behavioral defenses. Neurons in both regions sense core temperature and integrate central and peripheral thermal information. The setpoint temperature is then determined by relative synaptic inputs to warm-sensitive, cold-sensitive, and temperature-insensitive neurons. Fever is a regulated elevation in the preoptic setpoint temperature. Endogenous pyrogens and other fever mediators inhibit preoptic warm-sensitive neurons that normally facilitate heat loss and suppress heat production. This elevates the setpoint temperature for all thermoregulatory responses and activates cold-defenses such as vasoconstriction (which decreases heat loss) and shivering (which increases metabolic heat production). When pyrogen concentrations decrease, the setpoint temperature returns towards normal, triggering active vasodilation and sweating, which increases heat loss from the skin surface. The increasing phase of fever is often associated with shivering, which can markedly increase heart rate and cardiac output. Defervescence (and passive hyperthermia) is also often accompanied by tachycardia resulting from active precapillary vasodilation. Thus, cardiovascular complications are common throughout the febrile course and constitute the major clinical consequence of fever.