The set point has been used to define the regulated level of body temperature, suggesting that displacements of core temperature from the set point initiate heat production (HP) and heat loss (HL) responses. Human and animal experiments have demonstrated that the responses of sweating and shivering do not coincide at a set point, but rather establish a thermoeffector threshold zone. Neurophysiological studies have demonstrated that the sensor-to-effector pathways for heat production and heat loss overlap, and in fact mutually inhibit each other. This reciprocal inhibition theory, presumably reflecting the manner in which thermal factors contribute to homeothermy in humans, does not incorporate the effect of non-thermal factors on temperature regulation. The present review examines the actions of these non-thermal factors within the context of neuronal models of temperature regulation, suggesting that examination of these factors may provide further insights into the nature of temperature regulation. It is concluded that, though there is no evidence to doubt the existence of the HP and HL pathways reciprocally inhibiting one another, it appears that such a mechanism is of little consequence when comparing the effects of non-thermal factors on the thermoregulatory system, since most of these factors seem to exert their influence in the region after the reciprocal cross inhibition. At any given moment, both thermal and several non-thermal factors will be acting on the thermoregulatory system. It may, therefore, not be appropriate to dismiss the contribution of either, when discussing the regulation of body temperature in humans.