This chapter is going to dene these terms, review the concepts of Hans Selye’s model of General Adaptation, and Bruce McEwen’s allostatic load as they relate to depression. It will review stressresponse mechanisms in light of the hypothalamic-pituitary-adrenal axis. Additionally, treatment options related to stress and allostatic load will be reviewed. The chapter will conclude with a discussion of the prenatal environment’s culpability in the future offspring’s stress response in an effort to prevent depressive illness in the next generation.