Eicosanoids are a large group of oxygenated fatty acids [viz., omega-3 (n-3) and omega-6 (n-6) C(20) polyunsaturated fatty acids], the most important source being the omega-6 cell membrane-derived arachidonic acid (AA). Eicosanoids are produced by many different cell types; through their ligation and activation of specific membrane-bound and intracellular receptors, they regulate myriad physiological and pathological functions, including body temperature (T(b)). However, the thermoregulatory role of eicosanoids has mainly been associated with fever, i.e., with T(b) changes induced during illness; their importance in maintaining T(b) during health remains unclear. In this review, we address the question of whether AA-derived mediators (viz., prostaglandins, leukotrienes and other lipoxygenase metabolites, and the endocannabinoids/endovanilloids) are involved in normal (non-febrile) thermoregulation. We conclude that although prostaglandin E(2) is a principal mediator of fever, it is unlikely to be involved in the maintenance of normal T(b). Other eicosanoids reviewed also seem to have no major role in non-febrile thermoregulation. Newly discovered signaling pathways for eicosanoids, such as the endovanilloid system, may participate in thermoregulation, but further studies are required before definitive conclusions can be made.