The focus of this article is to review recent data concerning (1) the biological actions of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety, and depression by exploring pharmacological actions of the peptides in both rodents and humans and consequences of genetic or pharmacological blockade of the ghrelin/GHS-R system on these parameters, and (2) how ghrelin and ghrelin-derived peptides are regulated in human psychiatric disorders and animal models of psychiatric diseases such as eating disorders, anxio-depressive disorders, addiction to alcohol, and drugs of abuse. Here, GHRL is linked to major depressive disorder.