The control of cerebral blood flow (CBF) is critical in maintaining neuronal viability and cognitive processing. The endfeet of astrocytes surround the blood vessels of the brain and are now known to be important sites of communication with cerebral blood vessels. Recent research has indicated that astrocytes exhibit calcium signals in response to neuronal activity and release factors that modify CBF by eliciting vasoconstriction or vasodilation of arterioles. Work from our lab has shown the mechanisms by which these opposite astrocyte influences provide appropriate changes in vessel tone within a dynamic metabolic environment. The constriction results from the calcium dependent formation and release of arachidonic acid (AA) from astrocytes that induces constriction of smooth muscle cells. The dilation is from the conversion of AA to prostaglandin E2 (PGE2) that acts to relax smooth muscle cells and dilate arterioles. The ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E2, leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation. Manipulating this balance may be a therapeutic avenue for treating the inappropriate declines in cerebral blood flow that occur in some dementias and after stroke.