Neglect is a common and frequently chronic form of child maltreatment that can compromise child development and increase the risk of physical and psychological problems. In this review, we discuss one of the potential ways neglect becomes biologically embedded by shaping the development of a key stress responsive system: namely, the hypothalamic‐pituitary‐adrenal (HPA) axis. Several potential mediators and moderators of this process are examined, including inflammation, attachment and social buffering, self‐regulation, child sex and age, and genetics.