How complex physiological systems evolve is one of the major questions in evolutionary physiology. For example, how traits interact at the physiological and genetic level, what are the roles of development and plasticity in Darwinian evolution, and eventually how physiological traits will evolve, remains poorly understood. In this article we summarize the current frame of work evolutionary physiologists are employing to study the evolution of physiological adaptations, as well as the role of developmental and reversible phenotypic plasticity in this context. We also highlight representative examples of how the integration of evolutionary and developmental physiology, concomitantly with the mechanistic understanding of physiological systems, can provide a deeper insight on how endothermic vertebrates could cope with reduced ambient temperatures and oxygen availability characteristic of high altitude environments. In this context, high altitude offers a unique system to study the evolution of physiological traits, and we believe much can be gained by integrating theoretical and empirical knowledge from evolutionary biology, such as life-history theory or the comparative method, with the mechanistic understanding of physiological processes