The response of cerebral vasculature to exercise is different from other peripheral vasculature; it has a small vascular bed and is strongly regulated by cerebral autoregulation and the partial pressure of arterial carbon dioxide (Pa(CO(2))). In contrast to other organs, the traditional thinking is that total cerebral blood flow (CBF) remains relatively constant and is largely unaffected by a variety of conditions, including those imposed during exercise. Recent research, however, indicates that cerebral neuronal activity and metabolism drive an increase in CBF during exercise. Increases in exercise intensity up to approximately 60% of maximal oxygen uptake produce elevations in CBF, after which CBF decreases toward baseline values because of lower Pa(CO(2)) via hyperventilation-induced cerebral vasoconstriction. This finding indicates that, during heavy exercise, CBF decreases despite the cerebral metabolic demand. In contrast, this reduced CBF during heavy exercise lowers cerebral oxygenation and therefore may act as an independent influence on central fatigue. In this review, we highlight methodological considerations relevant for the assessment of CBF and then summarize the integrative mechanisms underlying the regulation of CBF at rest and during exercise. In addition, we examine how CBF regulation during exercise is altered by exercise training, hypoxia, and aging and suggest avenues for future research.