Integration of the hypothalamic–pituitary–adrenal (HPA) axis and the limbic system through glucocorticoid signaling is imperative in initiating and regulating a suitable stress response following real or perceived threats. Dysfunction of these circuits that results in a persistent or inhibited glucocorticoid secretion can severely affect processing of stressful experiences and lead to risk for developing further psychiatric pathology. Exposure to toxic chemicals found in our environment, including pesticides, metals, and industrial compounds, have been shown to have significant impact on neurological health and disease. Indeed, studies have begun to identify the HPA axis and limbic system as potential targets of many of these environmental chemicals, suggesting a possible environmental risk for damage to the stress circuit and response to stressful stimuli. This review will focus on our current understanding of the impact exposure to environmental toxicants, including bisphenol A and lead, has on the synaptic physiology of the HPA axis and limbic system and how this contributes to an alteration in behavior output. Further, this discussion will provide a starting point to continue to couple novel toxicological and neurological approaches to elaborate our understanding of the influence of environmental chemicals on the stress response and pathology.