We outline the mechanisms currently thought to be responsible for controlling cerebral blood flow (CBF) in the physiologic state and during ischemia, focusing on the arterial pial and penetrating microcirculation. Initially, we categorize the cerebral circulation and then review the vascular anatomy. We draw attention to a number of unique features of the cerebral vasculature, which are relevant to the microcirculatory response during ischemia: arterial histology, species differences, collateral flow, the venous drainage, the blood-brain barrier, astrocytes and vascular nerves. The physiology of the arterial microcirculation is then assessed. Lastly, we review the changes during ischemia which impact on the microcirculation. Further understanding of the normal cerebrovascular anatomy and physiology as well as the pathophysiology of ischemia will allow the rational development of a pharmacologic therapy for human stroke and brain injury.