The growth hormone secretagogue receptor (GHS-R) is expressed in several tissues and seems to mediate the different actions of the synthetic growth hormone secretagogues (GHS) and the endogenous ligand of this receptor, ghrelin. The GHS-R belongs to the family of G-protein coupled receptors (GPCR). Two different receptor variants, type 1a and 1b, have been described and they seem to mediate different actions in different tissues. In addition to their functions on growth hormone (GH) secretion and food intake, ghrelin and its receptor are involved in several cardiovascular mechanisms, pancreatic functions, adipogenesis, gonadal function, immune system actions or tumoral cells. This review will summarize data regarding the structure of the GHS-R gene, reports investigating the expression, control and functions of the GHS-R in various tissues, and studies of the underlying transcriptional mechanisms and the genetic manipulation of both ghrelin and GHS-R. Thus, it seems clear the possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact.