Although many studies have modeled the effects of climate change on future species distributions and extinctions, the theoretical approach most commonly used-climate envelope modeling-typically ignores the potential physiological capacity of animals to respond to climate change. We explore the consequences of the phenotypic plasticity available to animals, by examining physiological responses of free-living animals in their natural habitats and by applying integrative, mechanistic models of heat exchange in invertebrates and humans. Specifically, we explore how behavioral, autonomic, and morphological modifications such as nocturnal activity, selective brain cooling, and body color may potentially serve as buffers to the consequences of climate change. Although some species may adapt to climate change through phenotypic plasticity, there are significant limits to this strategy. Furthermore, predictions of the response of organisms to changes in climate can be erroneous when modeled at large scales using coarse spatial or temporal data. Environmental heterogeneity can provide habitats suitable for species even though large-scale changes in the climate might predict a species' extinction. A detailed understanding of physiology, combined with integrative biophysical modeling and ecological manipulation, provides a powerful tool for predicting future ecological patterns and managing their consequences.