Systems paleobiology seeks to interpret the history of life within the framework of Earth’s environmental history, using physiology as the conceptual bridge between paleontological and geochemical data sets. In some cases, physiological performance can be estimated directly and quantitatively from fossils—this is commonly the case for vascular plant remains. In other instances, statistical inferences about physiology can be made on the basis of phylogenetic relationships. Examples from research in paleobotany, marine micropaleontology, and invertebrate paleontology illustrate how physiological observations, experiments, and models can link biological radiations and extinctions to both long-term environmental trajectories and transient perturbations to the Earth system. The systems approach also provides a template for evaluating the habitability of other planets, not least of which is the ancient surface of Mars. Expanding physiological research motivated by concerns about our environmental future provides an increasing diversity of tools for understanding the relationship between Earth and life through time. The geologic record, in turn, provides critical input to research on contemporary global change.