Widespread recognition of the importance of biological studies at large spatial and temporal scales, particularly in the face of many of the most pressing issues facing humanity, has fueled the argument that there is a need to reinvigorate such studies in physiological ecology through the establishment of a macrophysiology. Following a period when the fields of ecology and physiological ecology had been regarded as largely synonymous, studies of this kind were relatively commonplace in the first half of the twentieth century. However, such large-scale work subsequently became rather scarce as physiological studies concentrated on the biochemical and molecular mechanisms underlying the capacities and tolerances of species. In some sense, macrophysiology is thus an attempt at a conceptual reunification. In this article, we provide a conceptual framework for the continued development of macrophysiology. We subdivide this framework into three major components: the establishment of macrophysiological patterns, determining the form of those patterns (the very general ways in which they are shaped), and understanding the mechanisms that give rise to them. We suggest ways in which each of these components could be developed usefully. © 2009 by The University of Chicago.