Amylin controls nutrient fluxes by reducing food intake, slowing gastric emptying and reducing postprandial glucagon secretion via a direct effect on the area postrema (AP). In the AP, amylin seems to modulate the anorectic signal elicited by cholecystokinin (CCK). Amylin’s excitatory action on AP neurons and its anorectic effect may depend on diet composition because rats fed protein as exclusive energy source showed a blunted response to amylin. In addition to a role in satiation (“episodic signal”), recent studies suggest that amylin may also play a role as an adiposity (“tonic”) signal. Similar to leptin or insulin, an elevated brain level of amylin resulted in lower body weight gain than in controls. This may also in part be due to an increase in energy expenditure. Overall, amylin may be an interesting target as a body weight lowering drug. Recent studies provided evidence that amylin, especially when combined with insulin, leptin or PYY has long-term effects on food intake and body weight in humans.