The gastrointestinal "hunger" hormone ghrelin is the only known circulating peripheral molecule with the ability to decrease body fat utilization and to increase body weight gain. Accordingly, due to ghrelin's effects to promote food intake while decreasing energy expenditure ghrelin may offer potential as a drug for treatment of eating/wasting disorders and cachexia. Therapeutic potential of ghrelin and ghrelin analogues to promote food intake and body weight gain was recently indicated in several clinical studies. The recent discovery of the ghrelin O-acyltransferase as the key enzyme responsible for ghrelin acylation has further deepened our understanding of ghrelin activation, thereby paving the way for more efficient targeting of the ghrelin pathway. Here, we summarize the current knowledge pertaining to the potential of the endogenous ghrelin system as a drug target for the treatment of eating/wasting disorders and cachexia.