This article in the Neural and Endocrine Section of Comprehensive Physiology discusses the physiology and pathophysiology of the pancreatic hormone amylin. Shortly after its discovery in 1986, amylin has been shown to reduce food intake as a satiation signal to limit meal size. Amylin also affects food reward, sensitizes the brain to the catabolic actions of leptin, and may also play a prominent role in the development of certain brain areas that are involved in metabolic control. Amylin may act at different sites in the brain in addition to the area postrema (AP) in the caudal hindbrain. In particular, the sensitizing effect of amylin on leptin action may depend on a direct interaction in the hypothalamus. The concept of central pathways mediating amylin action became more complex after the discovery that amylin is also synthesized in certain hypothalamic areas but the interaction between central and peripheral amylin signaling remains currently unexplored. Amylin may also play a dominant pathophysiological role that is associated with the aggregation of monomeric amylin into larger, cytotoxic molecular entities. This aggregation in certain species may contribute to the development of type 2 diabetes mellitus but also cardiovascular disease. Amylin receptor pharmacology is complex because several distinct amylin receptor subtypes have been described, because other neuropeptides [e.g., calcitonin gene-related peptide (CGRP)] can also bind to amylin receptors, and because some components of the functional amylin receptor are also used for other G-protein coupled receptor (GPCR) systems.