Future environments may resemble conditions that have not existed for millions of years. To assess the adaptive options available to organisms evolving under such circumstances, it is instructive to probe paleophysiology, the ways in which ancient life coped with its physical and chemical surroundings. To do this, we need reliable proxies that are based on fundamental principles, quantitatively verified in living species, and observable in fossil remains. Insights have already come from vertebrates and plants, and others will likely emerge for marine animals if promising proxies are validated. Many questions remain about the circumstances for the evolution of environmental tolerances, metabolic rates, biomineralization, and physiological responses to interacting species, and about how living organisms will perform under exceptional conditions.