In terms of its anatomical distribution, serotonin is strategically placed to affect the cerebral vasculature as it is located on both sides of the neuronal–vascular axis. The serotonin system consists of clusters of neurons containing 5-HT that have extensive projections to virtually all areas of the brain. The ascending tracts, originating mainly from the dorsal and median raph6 nuclei, congregate initially in the medial forebrain bundle before dividing into specific pathways. The primary targets are the hypothalamus, olfactory bulb, thalamus, caudate putamen, hippocampus, and cerebral cortex. The principal features of this system are its topographical organization, its high divergence, and its very high density of cortical projections. Such a complex system cannot be expected to have a “single” function, a fact that is underlined by the existence of at least 16 subtypes of 5-HT receptors, almost all present within the central nervous system. Probably this monoaminergic system acts as a neuromodulator that can either depress or activate certain physiological functions that may include those mechanisms that link brain function to blood flow.