The study of the proteome in response to environmental change is beginning to generate a number of new hypotheses about how organisms respond and adapt to a variety of stressors. The contributions to this symposium highlight how comparisons at the levels of species, populations, and tissues provide exciting new perspectives on the diversity of biochemical responses involved in the tolerance of stress. Despite limited genomic information, a number of studies of nonmodel organisms provide insights that are only accessible through a systems approach like proteomics. The realization that these systemic responses differ among closely related species, populations, and tissues illustrates the potential importance of the proteome to an organism's evolutionary response to a rapidly changing environment. Changes in an organism's proteome may occur as early as during the first stages of development and continue through acclimatization of the adult and adaptation of the following generations. A proteomic approach can also demonstrate how pollutants have systemic effects that may be counter-intuitive to expectations, emphasizing how isolating a single mode of action for a pollutant, e.g., xeno-androgen, is often inadequate. To continue with the progress made, we need a critical evaluation of the experimental designs used in proteomics studies, a reevaluation of some of the statistical analyses, and new technical advances in order to identify a greater number of proteins. The contributions to the current symposium offer the novice a starting point for assessing the potential of proteomics to generate novel hypotheses about how organisms interact with their environment.