The serotonin (5-HT)1B receptor is expressed in the central nervous system (CNS) of rodents and its homologous 5-HT1D beta receptor is expressed in human. These receptors are distributed in both serotonergic and non-serotonergic neurons, where they act as auto- or heteroreceptors, respectively. Studies from ours and other laboratories have shown that 5-HT1B receptors are densely expressed in the ventral pallidum, globus pallidus, substantia nigra and dorsal subiculum and moderately expressed in the cerebral cortex, the molecular layer of the hippocampus, the entopeduncular nucleus, the superficial gray layer of the superior colliculus, the caudate putamen and the deep nuclei of the cerebellum. At the ultrastructural level, 5-HT1B receptors were found distributed in axons and axon terminals and these receptors are located on the plasma membrane of unmyelinated axon terminals and in the cytoplasm close to the plasmalemma. The terminal localization of the 5-HT1B receptors in CNS suggests that there is a signal responsible for the protein transport toward the nerve terminals. Studies from ours and other groups using lesion, radioligand binding sites, viral transfection and anterograde methods have shown that 5-HT1B receptors are located at the nerve terminals of different pathways. The 5-HT1B receptors act as terminal receptors and are involved in regulation of the release of various neurotransmitters, including 5-HT itself. The regulation of gamma-aminobutyric acid release by 5-HT1B receptors has been found in projections: from caudate putamen to the globus pallidus or substantia nigra, from nucleus accumbens to the ventral tegmentum area, and from purkinje neurons to the deep nuclei of the cerebellum. The control of glutamate release by 5-HT1B receptors has been found in projections from hippocampus to the dorsal subiculum and of N-acetyl-aspartyl-glutamate release from retinal ganglion cells to the superficial gray layer of the superior colliculus. The control of 5-HT release by 5-HT1B receptors was shown in projections arising from the raphe nuclei to fore- and midbrain regions. Multiple evidences suggest that 5-HT1B receptors are implicated in several physiological functions, behavior and psychiatric diseases including migraine, locomotor activity, drug abuse reinforcement, migraine, aggressive behavior, depression and anxiety states.