Adversity experienced in early life can have detrimental effects on physical and mental
health. One pathway in which these effects occur is through the hypothalamic-pituitary-adrenal (HPA)
axis, a key physiological stress-mediating system. In this review, we discuss the theoretical perspec-
tives that guide stress reactivity and regulation research, the anatomy and physiology of the axis, de-
velopmental changes in the axis and its regulation, brain systems regulating stress, the role of genetic
and epigenetics variation in axis development, sensitive periods in stress system calibration, the social
regulation of stress (i.e., social buffering), and emerging research areas in the study of stress physiolo-
gy and development. Understanding the development of stress reactivity and regulation is crucial for
uncovering how early adverse experiences influence mental and physical health.