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A compromised autophagy is associated with the onset of obesity, type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases. Our aim is to review the potential role of ghrelin, a gut hormone involved in energy homeostasis, in the regulation of autophagy.In the recent years, it has been demonstrated that autophagy constitutes an important mechanism by which ghrelin exerts a plethora of central and peripheral actions. Ghrelin enhances autophagy through the activation of AMP-activated protein kinase in different target organs to regulate lipid and glucose metabolism, the remodeling and protection of small intestine mucosa, protection against cardiac ischemia as well as higher brain functions such as learning and memory consolidation. Nonetheless, in inflammatory states, such as acute hepatitis, liver fibrosis or adipose tissue inflammation, ghrelin acts as an anti-inflammatory factor reducing the autophagic flux to prevent further cell injury. Interestingly, several cardiometabolic disorders, including obesity, type 2 diabetes, nonalcoholic fatty liver disease or chronic heart failure are accompanied by low ghrelin levels in addition to altered autophagy.Ghrelin represents an attractive target for development of therapeutics for prevention or treatment of metabolic, cardiac or neuronal disorders, in which autophagy is impaired.