It is well established in animal models that the prenatal environment can have a major impact on stress axis function throughout life. These changes can predispose to various metabolic, cardiovascular, and neurobiological pathophysiologies. Emerging evidence indicates that the same programming effects occur in humans. It is now becoming clear that the pathophysiological effects are not confined to the first-generation offspring and that there is transgenerational memory of fetal experience that can extend across multiple generations. The complex mechanisms by which transgenerational transmission of stress responsiveness occur are rapidly becoming a focus of investigation. Understanding these fundamental biological processes will allow for development of intervention strategies that prevent or reverse adverse programming of the stress response.