Functional hyperemia – the linkage between neuronal activity and local blood flow that serves to satisfy neuronal metabolic demands – is a phenomenon that has been appreciated for over 100 years; however, the underlying mechanisms are poorly understood. Recent studies have illuminated a potentially central role for astrocytic calcium (Ca²⁺) signals as mediators of this process. Astrocytes make hundreds to thousands of contacts with neurons, and their processes (‘endfeet’) encase the brain microcirculation. Neuronal stimulation causes a rapid elevation in intracellular Ca²⁺ which propagates to the endfeet, and is associated with subsequent reduction in Ca²⁺ in the smooth muscle cells (SMCs) of the penetrating arterioles (Filosa et al. 2004). Utilizing high spatiotemporal resolution confocal calcium imaging of cortical brain slices, it was found that inositol trisphosphate (InsP₃R) receptors are present within astrocytic endfeet and are activated following induction of neuronal activity. The generation of an endfoot-delimited Ca²⁺ increase in an individual endfoot, through rapid spatially restricted photo-release of caged InsP₃, was sufficient to induce local vasodilatation of an adjacent arteriole (Straub et al. 2006). Since the InsP₃-induced vasodilatation was restricted to a short stretch of the vessel centred on the endfoot, it suggests that endfeet function as individual ‘vasoregulatory units’ in the brain. One potential target for a Ca²⁺ signal in the astrocytic endfoot is the large-conductance, Ca²⁺-sensitive K⁺ (BK) channel, which when activated would release K⁺ ions from the endfoot onto the adjacent smooth muscle of the arteriole. Modest elevation of extracellular potassium (K⁺) activated inward rectifier K⁺ (Kir) channels, and caused membrane potential hyperpolarization and vasodilatation of intracerebral arterioles, in isolation, and in cortical brain slices. Blocking Kir channels or BK channels reduced neuronally-evoked vasodilatation by about 70%, and caused complete abrogation in the presence of a COX inhibitor (Filosa et al. 2006). These results support the concept that neuronal activity is translated into an InsP₃-mediated calcium signal in astrocytes, which is decoded by BK channels in the endfoot to locally release K⁺ into the perivascular space to activate SM Kir channels, and cause vasodilatation.