During early life-sensitive periods (i.e., fetal, infancy), the developing stress response system adaptively calibrates to match environmental conditions, whether harsh or supportive. Recent evidence suggests that puberty is another window when the stress system is open to recalibration if environmental conditions have shifted significantly. Whether additional periods of recalibration exist in adulthood remains to be established. The present paper draws parallels between childhood (re)calibration periods and the perinatal period to hypothesize that this phase may be an additional window of stress recalibration in adult life. Specifically, the perinatal period (defined here to include pregnancy, lactation, and early parenthood) is also a developmental switch point characterized by heightened neural plasticity and marked changes in stress system function. After discussing these similarities, lines of empirical evidence needed to substantiate the perinatal stress recalibration hypothesis are proposed, and existing research support is reviewed. Complexities and challenges related to delineating the boundaries of perinatal stress recalibration and empirically testing this hypothesis are discussed, as well as possibilities for future multidisciplinary research. In the theme of this special issue, perinatal stress recalibration may be a mechanism of multilevel, multisystem risk, and resilience, both intra-individually and intergenerationally, with implications for optimizing interventions.