Developmental psychology is rapidly becoming a neuropsychobiological field concerned with understanding how the genes we are born with, the experiences we have that modify gene expression, and the physiological responses in our brains and bodies all come together to write the story of our lives. Nowhere is the importance of a multilevel, multidisciplinary, genes‐to‐society perspective more apparent than in the study of stress and its role in development. This chapter focuses on a key stress‐mediating system, the hypothalamic‐pituitary‐adrenocortical (
HPA
) axis, its development and regulatory processes, its effects on brain systems involved in emotion and cognition, and its interactions with other stress‐mediating systems. The normative development of the
HPA
axis is described, along with the role of temperament as a moderator of stress responding and stress effects. The majority of the chapter summarizes evidence that the
HPA
axis plays a role in the biological embedding of experience during development, including questions about developmental plasticity and developmental programming in relation to poverty, prenatal stress, parental loss, risky family environments, and maltreatment. The role of the
HPA
axis in developmental psychopathology is also discussed. Future directions and fruitful areas of research are considered with each topic.