Abstract: The human brain has exceedingly high metabolic demands. The cerebral vasculature has the critical task of providing sufficient blood supply to meet this demand. The sudden interruption of blood flow to the brain, as observed during ischemic stroke, results in acute neurological injury with devastating consequences – a high rate of adult disability and death. Ischemic stroke is thus a vascular disorder with a dramatic neurological impact. There is an urgent need for more effective disease management to combat stroke as current treatment paradigms, focusing on vascular recanalization and neuroprotection, have only limited clinical success. Since accumulating data suggests successful long-term neuroprotection is unlikely to be achievable without a functional microvascular network, strategies that reduce endothelial dysfunction could be indispensable. Encouragingly, very recent evidence highlighted herein suggests protecting the humble pericyte may be a new approach to reaching this goal.