Global change includes alterations in ocean temperature, oxygen availability, salinity, and pH, abiotic variables with strong and interacting influences on the physiology of all taxa. Physiological stresses resulting from changes in these four variables may cause broad biogeographic shifts as well as localized changes in distribution in mosaic habitats. To elucidate these causal linkages, I address the following questions: What types of physiological limitations can alter species' distributions and, in cases of extreme stress, cause extinctions? Which species are most threatened by these physiological challenges--and why? How do contents of genomes establish capacities to respond to global change, notably in the case of species that have evolved in highly stable habitats? How fully can phenotypic acclimatization offset abiotic stress? Can physiological measurements, including new molecular ("-omic") approaches, provide indices of the degree of sublethal stress an organism experiences? And can physiological evolution keep pace with global change?