Multiple and complex interactions exist between the cerebral circulation and a potent vasoactive (and neurotransmitter) agent, serotonin. The nature and bases of the real and potential relationships are often hotly contested, for example, the serotonergic innervation of brain conducting and resistance vessels. In this review, an attempt is made to reconcile the available literature and to indicate future and possibly fruitful research directions. It appears that, by its very nature, the pattern of the serotonergic innervation is singular to blood vessels of the brain and could provide a neuronal link (or coupling) between functional events within the central nervous system and its perfusion which subserves changes in brain function. Finally, there are sufficient data to suggest an involvement of 5-hydroxytryptamine in different cerebrovascular pathologies.