Our internal and external environments are not stable; these ever-changing contexts produce stress on bodily systems. In response, the body recruits numerous peripheral hormones to bring those systems back within a desired homeostatic range. When our environments change in extreme ways and for prolonged periods of time, a different set of hormonal stress responses are recruited. These chronic stress responses produce adaptive changes but can also drive maladaptation. This chapter begins by reviewing the peripheral hormones that are recruited as part of the acute stress response and describing their adaptive impact on brain and peripheral function. We then examine new research describing the role of ghrelin, a hormone produced by the gut, in chronic stress. We review the role of ghrelin in hunger and consider how energy deficiency, a state shared by both hunger and stress, might explain why ghrelin is elevated by both. We consider how the unique recruitment of ghrelin during chronic stress mediates responses in the brain that can help an organism respond to future stressors, but also how chronic elevation of ghrelin can produce additional adaptations that contribute to stress-sensitive psychiatric disorders. Lastly, we identify important future areas for research on the biology of ghrelin.