The brain is a vital organ that relies on a constant and adequate supply of blood to match oxygen and glucose delivery with the local metabolic demands of active neurones. It is well established that cerebral blood flow is altered in response to both neural activity and humoral stimuli. Thus, augmented neural activation (e.g. visual stimulation) leads to locally increased cerebral blood flow via functional hyperaemia, whereas humoral stimuli (i.e. alterations in arterial PO₂ and PCO₂) produce global increases in cerebral blood flow. Perhaps not surprisingly, cerebrovascular responses to neural activity and humoral stimuli may not be highly correlated because they reflect different physiological mechanisms for vasodilation. Exquisite regulation of cerebral blood flow is particularly important under hypoxic conditions when cerebral PO₂ can be reduced substantially. Indeed, cerebrovascular reactivity to hypoxia determines the capacity of cerebral vessels to respond and compensate for a reduced oxygen supply. This reactivity is dynamic, changing with prolonged exposure to hypoxic environments, and in patients and healthy individuals exposed to chronic intermittent periods of hypoxia. More recently, a number of animal studies have provided evidence that glial cells (i.e. astrocytes) play an important role in regulating cerebral blood flow under normoxic and hypoxic conditions. This review aims to summarize our current understanding of cerebral blood flow control during hypoxia in humans and put into context the underlying neurovascular mechanisms that may contribute to this regulation.