Historically, the discipline of comparative physiology and biochemistry has had two major goals: (1) elucidation of mechanisms and their adaptative significance, and (2) understanding of the evolution of mechanisms and adaptations. In general, the first goal has dominated the field. In a mechanistic/adaptational approach, the diversity of organisms is an experimental parameter in the investigation. Lineage-specific characteristics reveal both how physiological systems work and how different kinds of animals are adapted to different kinds of environments. We believe that this approach is far from outdated, in part because many animal groups have been investigated superficially if at all, and in part because the incorporation of fundamentally new technologies into our discipline permits us to address previously intractable questions about even intensively studied animal groups. In evolutionary physiology and biochemistry, the diversity of lineage-specific physiological systems and how they came to be is the subject of investigation. Early attempts to employ the evolutionary approach were not only few in number, they were unsatisfying in outcome because neither phylogenetic nor mechanistic/adaptational knowledge was adequate to serve as a firm foundation. We agree with earlier authors that new and more sophisticated applications of this approach, together with progress in understanding both animal phylogeny and mechanisms/adaptations, all promise to allow us at last to fulfill our second historic goal. In our view, an integration of the two approaches seems to present the most productive trajectory into the next century.