The discovery of adrenal steroid receptors outside of the hypothalamus in the hippocampus and other forebrain regions catalyzed research on the effects of stress upon cognitive function, emotions and self-regulatory behaviors as well as the molecular, cellular and neuroanatomical mechanisms underlying acute and chronic stress effects on the brain. Indeed, this work has shown that the brain is a plastic and vulnerable organ in the face of acute and chronic stress. The insight that Bob and Caroline Blanchard had in developing and interpreting findings using the Visible Burrow System model made an enormous contribution to the current view that the human brain is very sensitive to the social environment and to agonistic interactions between individuals. Their collaboration with Sakai and McEwen at The Rockefeller University extended application of the Visible Burrow System model to demonstrate that it also was a unique and highly relevant neuroethological model with which to study stress and adaptation to stressors. Those studies focused on the brain and systemic organ responses to stress and, in turn, described that the brain is also very responsive to changes in systemic physiology.