Decades of human and animal research demonstrates that stress responsive neuroendocrine systems calibrate to the harshness of environmental conditions during fetal and early postnatal life. Emerging evidence indicates that if conditions change markedly over childhood, the hypothalamic pituitary adrenal (HPA) axis may recalibrate during puberty, another period that involves heightened neural plasticity and rapid maturation of neurobehavioral systems. These recent findings have prompted increased interest in the potential for stress system calibration/recalibration over development. To direct research in this area, this chapter integrates and discusses theoretical perspectives and empirical evidence pertaining to calibration and recalibration of the stress response. We describe how these concepts relate to other constructs, including sensitive periods, plasticity, and programming. We then consider four potential periods of calibration/recalibration: fetal, infancy, puberty, and pregnancy/lactation. In each section, we discuss evidence that the HPA and/or sympathetic medullary adrenal (SAM) system undergoes developmental change, rendering it more plastic and amenable to shift its activity in response to environmental conditions. We also review findings that the impacts of environmental harshness on stress responding persist beyond these periods. We then articulate that marked change in the quality of the environment (from harsh to benign or vice versa) is required in order for recalibration to occur, and that recalibration would result in shifts in stress responding to more closely align with the profiles of individuals who have experienced these conditions throughout life. Finally, we reflect on whether recalibration of the HPA and SAM system may extend to the other stress-responsive neurobehavioral systems.