Many vertebrates regulate their body temperature in response to thermal variability of the environment. Endotherms maintain relatively stable body temperatures by adjusting metabolic heat production in response to varying environmental heat loads. Although most ectotherms do not display adaptive thermogenesis, they do acclimate cellular metabolism to compensate for environmental temperature variation. The components of the thermoregulatory systems in endotherms and ectotherms are evolutionarily conserved, and I suggest that metabolic acclimation in ectotherms relies on the same regulatory pathways as adaptive thermogenesis in endotherms. Both groups rely on transient receptor potential ion channels to sense environmental temperatures. Thermosensory (afferent) information is relayed to the hypothalamus, which initiates a sympathetic efferent response. Cardiovascular responses to heat are similar in ectothermic crocodiles and in mammals, and are mediated by the autonomic nervous system in both cases. The sympathetic nervous system also modulates cellular metabolism by inducing expression of the transcriptional regulator peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha), which interacts with a range of transcription factors that control glycolysis, fatty acid oxidation, gluconeogenesis, mitochondrial biogenesis and bioenergetics, and metabolic rate. PGC-1alpha is best known from mammalian model species but there is increasing evidence that it is also instrumental in non-mammalian vertebrates. Hence, endothermic adaptive thermogenesis may result from the same regulatory pathways as ectothermic metabolic acclimation, and both could be considered as adaptive metabolic responses to temperature variation.