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Glucocorticoid hormones are considered potent modulators of trade-offs between reproduction and survival. As such, selection should affect glucocorticoid physiology, although relatively little is known about how selection may act on glucocorticoid profiles. In general, the evolution of physiology is less studied and less well understood than morphological or life history traits. Here, we used a long-term data set from a population of mountain white-crowned sparrows to estimate natural selection on glucocorticoid profiles. Our study suggests that survival selection favours higher hormone concentrations for multiple components of glucocorticoid physiology (both baseline and stress-induced glucocorticoid levels). Fecundity selection varies depending on the component of hypothalamic-pituitary-adrenal physiology; greater reproductive output was associated with higher baseline glucocorticoid levels, but lower stress-induced glucocorticoid levels. Additionally, the selection gradient was greater for glucocorticoids than for a morphological trait (wing length). These results support the hypothesis that stress-induced glucocorticoids increase survival over reproduction within a wild population (the CORT-trade-off hypothesis). Taken together, these results add to our knowledge of how selection operates on physiological traits and also provide an evolutionary and ecological perspective on several key open issues in the field of glucocorticoid physiology.