During the past several decades there has been increasing attention to the risks of exposure to endocrine disrupting chemicals, agents that mimic or block the effects of endogenous hormones. Previous research demonstrates that there may be critical periods of development where factors such as prenatal stress and endocrine disrupting chemical exposure can result in endocrine system dysregulation which manifests both immediately and later in life. This review describes the types of common endocrine disrupting chemicals and routes of exposure, the structure and functions of the hypothalamic-pituitary-adrenal axis and its role in the physiological response to stress, and highlights the current evidence showing that endocrine disrupting chemicals may alter normal hypothalamic-pituitary-adrenal axis functions. These topics are unified upon discussion of evidence indicating that prenatal endocrine disrupting chemical exposure has many of the same effects as prenatal stress on the hypothalamic-pituitary-adrenal axis, leading to long-term dysregulation of the axis and subsequent alterations in physiological responses to stress. We further suggest that prenatal endocrine disrupting chemical exposure in combination with prenatal stress may result in additive, if not synergistic effects on the hypothalamic-pituitary-adrenal axis-mediated stress response. Finally, we discuss vulnerable populations at an elevated risk for dual stress and endocrine disrupting chemical exposure and emphasize critical areas for future research.