Capillary pericytes regulate cerebral blood flow in health and disease. Neuronal activity and neurotransmitters like glutamate trigger pericyte relaxation, leading to capillary dilation. This process involves prostaglandin E2 and requires nitric oxide to suppress vasoconstricting 20-HETE synthesis. In vivo, capillaries dilate before arterioles, contributing to 84% of the blood flow increase. In ischaemia, pericytes constrict and die, potentially causing irreversible capillary constriction and blood-brain barrier damage. Pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Preventing pericyte constriction and death may reduce long-term blood flow decreases after stroke. Pericytes are contractile cells on capillaries that regulate blood flow, stabilize new capillaries, maintain the blood-brain barrier, and contribute to glial scars. They can be constricted or dilated by neurotransmitters, and capillary blood flow heterogeneity may reflect pericyte tone. Pericytes constrict in vivo but were previously thought not to relax. In pathology, pericytes may constrict blood flow. The study shows pericytes are the first vascular elements to dilate during neuronal activity, making them initiators of functional imaging signals. Pericytes die readily in ischaemia, promoting brain damage. Signalling regulating pericyte dilation involves prostaglandin E2 and nitric oxide. Pericytes increase blood flow in vivo, with capillaries dilating before arterioles. In ischaemia, pericytes constrict and die, leading to prolonged capillary constriction. Pericyte death is a rapid response to ischaemia, contributing to ongoing neuronal damage. Understanding pericyte regulation of blood flow is crucial for functional imaging and stroke therapy. Pericytes actively regulate blood flow, with capillaries contributing 84% of the blood flow increase. Pericyte death after ischaemia may explain long-term blood flow decreases after stroke. The study highlights the importance of pericytes in cerebral blood flow regulation and stroke treatment.Capillary pericytes regulate cerebral blood flow in health and disease. Neuronal activity and neurotransmitters like glutamate trigger pericyte relaxation, leading to capillary dilation. This process involves prostaglandin E2 and requires nitric oxide to suppress vasoconstricting 20-HETE synthesis. In vivo, capillaries dilate before arterioles, contributing to 84% of the blood flow increase. In ischaemia, pericytes constrict and die, potentially causing irreversible capillary constriction and blood-brain barrier damage. Pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Preventing pericyte constriction and death may reduce long-term blood flow decreases after stroke. Pericytes are contractile cells on capillaries that regulate blood flow, stabilize new capillaries, maintain the blood-brain barrier, and contribute to glial scars. They can be constricted or dilated by neurotransmitters, and capillary blood flow heterogeneity may reflect pericyte tone. Pericytes constrict in vivo but were previously thought not to relax. In pathology, pericytes may constrict blood flow. The study shows pericytes are the first vascular elements to dilate during neuronal activity, making them initiators of functional imaging signals. Pericytes die readily in ischaemia, promoting brain damage. Signalling regulating pericyte dilation involves prostaglandin E2 and nitric oxide. Pericytes increase blood flow in vivo, with capillaries dilating before arterioles. In ischaemia, pericytes constrict and die, leading to prolonged capillary constriction. Pericyte death is a rapid response to ischaemia, contributing to ongoing neuronal damage. Understanding pericyte regulation of blood flow is crucial for functional imaging and stroke therapy. Pericytes actively regulate blood flow, with capillaries contributing 84% of the blood flow increase. Pericyte death after ischaemia may explain long-term blood flow decreases after stroke. The study highlights the importance of pericytes in cerebral blood flow regulation and stroke treatment.