Ghrelin plays a key role as the major orexigenic hormone from the gastrointestinal tract to the hypothalamic areas that govern food intake, balancing against a multitude of anorectic hormones, such as leptin, insulin and PYY3–36. Surprisingly, even in the absence of agonist, the ghrelin receptor signals with ∼50% activity. Thus, although ghrelin receptor antagonists are expected to reduce meal-associated food intake, inverse agonists of the ghrelin receptor, by blocking the constitutive receptor activity, might lower the set-point for hunger between meals, eliminating the craving for second orders, desserts and snacks.