Emerging technologies in genomics (e.g., cDNA library screening, DNA arrays), proteomics (e.g., two-dimensional gel electrophoresis and mass-spectroscopy fingerprinting), and metabolic regulation (e.g., elucidating protein-protein binding associations or signal transduction pathways) offer powerful tools for comparative biochemistry that will greatly increase our understanding of how animals adapt to environmental stress. The power of these new technologies and their potential application for physiological and ecophysiological research are illustrated with examples of recent advances in key fields. These include hypoxia/anoxia-responsive gene expression, the actions and regulation of the hypoxia-inducible transcription factor, the central role of the AMP-dependent kinase in mediating cellular responses to changing energy status, mammalian target of rapamycin mediation of nutrient signals in the control of protein synthesis and growth, proteomics approaches to identifying the physiological substrates of protein kinases, and the interactions of biochemistry and physiology in determining a net organismal response to high hematocrit values stimulated by erythropoietin. In particular, gene- and protein-screening technologies will drive a fundamental shift in the way that environmental stress effects on metabolism are evaluated by providing a holistic overview of the responses of a huge range of cell functions to stress and allowing researchers to identify multiple new areas of metabolic response that contribute to biochemical and physiological adaptation.