Perturbations of the environment result in activation of the hypothalamo-pituitary-adrenal axis (HPA) and an increase in glucocorticoid secretion that triggers the emergency life history stage (EHLS). This stage regulates behavioural and physiological responses that promote self preservation at the expense of regular life history stages such as breeding. This adrenocortical response to perturbations is found from fish to humans. Field and laboratory evidence indicates that the adrenocortical response to perturbations can be modulated according to season, life history stage and sex in many vertebrates. In the Gambel’s white-crowned sparrow the adrenocortical responses to a standardized experimental perturbation (capture, handling and restraint), are up-regulated at, and soon after, arrival on the breeding grounds in males, but much less so in females. Once nesting is initiated, the adrenocortical responses are down-regulated in both sexes. The increased activity of the HPA axis at arrival provides behavioural and physiological flexibility at a time of extreme weather conditions, but once nesting is initiated then responses of the HPA axis to perturbations are suppressed to maximize reproductive success. Experimental evidence reveals that the sensitivity to negative feedback of corticosterone is decreased at arrival in males but not females. Furthermore, plasma levels of corticosterone-binding globulin also increase at this time perhaps providing a buffer to protect against high corticosteroid levels. Modulation of the HPA axis appears to be at the hypothalamic level or higher accompanied by changes in mineralocorticoid receptor gene expression in the hypothalamus. Modulation of the HPA axis and the response to perturbations may be critical to maximize flexibility and self preservation before nesting begins, but then are down-regulated to enhance reproductive success.