After defining hyperthermia and fever, this article describes the complete chain of events leading to the genesis of fever, starting with the lipopolysaccharide-induced formation of endogenous pyrogens (cytokines), their interactions with relevant targets in the brain, the induction of enzymes responsible for the formation of prostaglandin E2, the activation of descending neuronal pathways via the EP3 receptor, and the stimulation of thermogenesis via this pathway to support the febrile shift of the thermoregulatory set point. This article also summarizes an alternative hypothesis to account for a rapid induction of the early phase of lipopolysaccharide-induced fever before the release of larger amounts of cytokines into the bloodstream. Other topics discussed include malignant hypothermia, drug-induced hypothermia, and the heat stroke syndrome.