Background Research on early adversity, stress biology, and child development has grown exponentially in recent years. Findings We review the current evidence for the hypothalamic–pituitary–adrenocortical (HPA) axis as a stress‐mediating mechanism between various forms of childhood adversity and psychopathology. We begin with a review of the neurobiology of the axis and evidence for relations between early adversity–HPA axis activity and HPA axis activity–psychopathology, as well as discuss the role of regulatory mechanisms and sensitive periods in development. Conclusions We call attention to critical gaps in the literature to highlight next steps in this research including focus on developmental timing, sex differences, stress buffering, and epigenetic regulation. A better understanding of individual differences in the adversity–HPA axis–psychopathology associations will require continued work addressing how multiple biological and behavioral systems work in concert to shape development.