In order to survive and thrive, organisms must adapt to constantly changing environmental pressures. When there are significant shifts in the environment, the brain and body engage a set of physiological and behavioral countermeasures collectively known as the “stress response”. These responses, which include changes at the cellular, systems, and organismal level, are geared toward protecting homeostasis and adapting physiological operating parameters so as to enable the organism to overcome short-term challenges. It is the shift of these well-organized acute responses to dysregulated chronic responses that leads to pathologies. In a sense, the protective measures become destructive, causing the myriad health problems that are associated with chronic stress. To further complicate the situation, these challenges need not be purely physical in nature. Indeed, psychosocial stressors such as ruminating about challenges at work, resource insecurity, and unstable social environments can engage the very same emergency threat systems and eventually lead to the same types of pathologies that sometimes are described as “burnout” in humans. This short review focuses on very recent empirical work exploring the effects of chronic stress on key brain circuits, metabolism and metabolic function, and immune function.