Through an assembly of interacting GPCRs, heterodimers and high-order heteromers (termed receptor mosaics) are formed and lead to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. This field has now become a major research area, and this review deals with their physiology being integrators of receptor signaling in the CNS and their use as targets for novel drug development based on their unique pharmacology.