Aerobic performance is tied to fitness as it influences an animal’s ability to find food, escape predators, or survive extreme conditions. At high altitude, where low oxygen availability and cold prevail, maximum metabolic heat production (thermogenesis) is an aerobic performance trait that is intimately linked to survival. In this seminar, I discuss the evolution of thermogenic performance in the North American deer mouse (Peromyscus maniculatus), a cosmopolitan rodent that can be found from lowland prairies to the highest peaks in North America. I show that high-altitude deer mice have evolved enhanced thermogenic performance, and then detail what we know about the physiological and genetic mechanisms that underlie this enhancement. I also show that the ontogeny of thermogenesis is delayed at high altitude, and detail why this delay may involve an energetic trade-off. Overall, our results highlight that natural selection shapes aerobic performance at high-altitude across multiple, intersecting physiological systems.