Mitchell, DuncanFuller, AndreaSnelling, Edward P.Tattersall, Glenn J.Hetem, Robyn S.Maloney, Shane K.2025-06-022025-06-022025-06Mitchell, D., Fuller, A., Snelling, E.P. et al. 2025, 'Revisiting concepts of thermal physiology : understanding negative feedback and set-point in mammals, birds, and lizards', Biological Reviews, vol. 100, no. 3, pp. 1317-1346, doi : 10.1111/brv.70002.1464-7931 (print)1469-185X (online)10.1111/brv.70002http://hdl.handle.net/2263/102596The thermoregulatory system of homeothermic endotherms operates to attain thermal equilibrium, that is no net loss or gain of heat, where possible, under a thermal challenge, and not to attain a set-point or any other target body temperature. The concept of a set-point in homeothermic temperature regulation has been widely misinterpreted, resulting in such confusion that some thermoregulation specialists have recommended that it be abandoned. But the set-point concept has enjoyed a resurgence in a different domain, lizard microclimate selection. We review the principles of thermoregulation in homeotherms, endorse a negative feedback system with independent set-points for individual thermo-effectors as its core mechanism, and address the misconceptions about homeothermic set-point. We also explore the concept of set-point range in lizard microclimate selection and conclude that there is substantial convergence between that concept and the set-points of homeothermic thermo-effectors, as thresholds. In neither homeothermic nor lizard thermoregulation is the concept of a unitary set-point appropriate. We review the problems of measuring the set-points for lizard microclimate selection. We do not believe that the set-point concept in thermoregulation should be abandoned just because it has been misinterpreted by some users. It is a valid concept, identifying the threshold body temperatures at which regulatory thermo-effectors will be activated, to aid in attaining thermal equilibrium.en© 2025 The Author(s). Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.ThermoregulationBody temperatureHomeothermyPoikilothermyHypothalamusTransfer functionEvaporative coolingMicroclimate selectionProportional controlShuttle boxArticle