One of the most significant evolutionary advancements in vertebrates is the evolution of homeothermic endothermy. The ability to maintain a high and constant body temperature has freed endotherms from many of the metabolic effects of fluctuating temperature and allowed endotherms to inhabit a wide range of habitats. However, endothermy is very energetically costly and not an ideal solution for many vertebrates. Despite the drawbacks, endotherms have evolved many physiological adaptations to overcome the challenges posed by challenging environmental conditions. In this dissertation I investigate several physiological adaptations endotherms have evolved to deal with the challenges imposed by these environments. Mammals living in deserts must prevent hyperthermia while maintaining proper water balance. This is problematic because the only mechanism for cooling is to evaporate water, the scarcity of which defines desert habitats. I used a phylogenetic comparative analysis to show that mammals living in arid regions have evolved mechanisms to reduce rates of total evaporative water loss. In this analysis I used many continuous variables to describe habitat in addition to classifying habitats as arid or mesic. Mammals living in cold habitats must prevent hypothermia by increasing internal heat production, which requires increased energy intake, a problem confounded by the lack of primary productivity in cold habitats. Mammals can increase heat production either by increasing their capacity for shivering or nonshivering thermogenesis. I acclimated deer mice to cold ambient temperature to show that they can increase metabolic heat production by increasing their capacity for nonshivering thermogenesis. Endotherms living at high altitudes face a two-fold problem, cold temperatures combined with limited oxygen availability. The ability to maintain body temperature and aerobic activity is dependent on oxygen. The ability to carry excess oxygen in the blood would likely be beneficial to animals living at high altitude. I tested whether or not deer mice originally from high altitude have an excess ability to carry oxygen in their blood and found that the circulatory distribution of oxygen likely sets an upper limit for aerobic performance in these animals.