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Treatment of so-called civilization diseases, including some forms of cancer, immune-related diseases and metabolic disorders, represent a major challenge in the industrialized world. In addition to genetic predisposition, behavior and exposure to xenobiotics contribute to these diseases. Here, we review existing evidence for an association of environmental chemicals with disturbed glucocorticoid- and mineralocorticoid-regulated physiological processes. Impaired activity of glucocorticoids and mineralocorticoids can contribute to several diseases, including neurological diseases, immune disorders and metabolic syndrome. Recent studies provide evidence for the existence of environmental chemicals that are able to disrupt the function of these hormones at different levels of their action. Therefore, potential interferences with these hormones should be considered for safety assessment of chemicals. Compared with the extensive knowledge on chemicals interfering with estrogen or androgen responses, the study of glucocorticoid and mineralocorticoid disruptors is an emerging field of research, and the identification of relevant xenobiotics and their underlying mechanisms of toxicity remains a major challenge.