The ghrelin receptor is now known to play an important role in regulating physiological responses to stress. In particular, ghrelin acting at the growth hormone secretagogue receptor (ghrelin receptor) may promote anxious behaviours under non-stressed conditions, and attenuate anxiety under conditions of stress. Dysregulation of the ghrelin system therefore has significant consequences for stress-related mood disorders such as anxiety and depression; disorders that pose a substantial problem for human health. These effects of the ghrelin system on mood are of particular concern in obese populations, where the likelihood of a mood disorder is higher and the ghrelin system disrupted. Studies in humans are still revealing conflicting roles for ghrelin and the ghrelin receptor in anxiety and depression, but these, and studies in animal models, offer evidence that ghrelin may influence its receptor at extra-hypothalamic brain regions to exert indirect control over central responses to stress and over brain pathways related to anxiety and depression. In this chapter, I discuss the background and potential mechanisms for ghrelin and ghrelin receptor's role in regulating stress and stress-related mood disorders