Publisher Summary Despite a clear evidence for a distinct amylin pharmacology and the localization of such pharmacology to sites such as the nucleus accumbens, efforts to clone an amylin receptor were fruitless for over a decade. This enigma led many to doubt the status of amylin as a bona fide hormone. The enigma of the amylin receptor was solved following the identification of receptor activity modifying proteins (RAMPs). These single transmembrane spanning molecules, when associated with a calcitonin receptor, altered its pharmacology from calcitonin-preferring to amylin-preferring. The newly designated amylinomimetic drug class has been defined on the basis of its unique pharmacology prior to the molecular characterization of amylin receptors. Currently, the class includes any agent that acts as an agonist at characterized amylin receptors. Several peptides, typically analogs of truncated salmon calcitonin, have been developed as potent and selective amylin antagonists and have been useful in identifying amylinergic responses.