Animals occupy an impressive range of environments, and many approach the limits of conditions that are compatible with life. Such environments are often characterized by low productivity, and survival depends on abilities to maintain levels of hydration sufficient for biochemical reactions and an adequate level of energy turnover. Specific adaptations for acquiring and conserving water affect the intake and utilization of energy that is available for growth and reproduction. Almost any benign, historically stable environment can become hostile if conditions change, and the severity of challenges to animals depends on temporal as well as spatial factors that are related to the intensity and duration of harsh conditions (e.g., drought). Animals have responded to such changes through avoidance, phenotypically plastic adjustments, and evolutionary changes in genomic structure. Here we present an overview of research findings presented at a session of the Third International Conference of Comparative Physiology and Biochemistry. We hope such a synthesis will stimulate new directions in research that address biological responses to environmental change. In this context, we believe that challenging environments in Africa might provide increasingly useful sites for biological investigations relating to the application of comparative and evolutionary approaches toward a deeper understanding of physiological adaptation.