The mechanisms of central nervous respiratory and cardiovascular chemosensory function underlying detection of blood and brain pH and PCO2 levels are not completely understood. We hypothesised that astrocytes - the most abundant type of brain glial cells – may act as functional brain chemosensors. Indeed, by having contacts with cerebral vasculature as well as multiple neurons, astrocytes are in a position to 'taste' the chemical composition of the arterial blood entering the brain and integrate this information with that of brain parenchyma. We found that astrocytes which reside within the 'classical' brainstem chemoreceptor areas located near the ventral surface of the medulla oblongata are highly chemosensitive. They respond to small physiological decreases in pH with vigorous elevations in intracellular Ca²⁺ and release of ATP. ATP spreads astroglial Ca²⁺ excitation within the neuropil, activates key chemoreceptor neurons and respiratory neurons of the medullary rhythm-generating circuits and induces adaptive increases in breathing. During systemic hypoxia, ATP is also released and acts to maintain respiratory activity in conditions when hypoxia-induced depression of respiration occurs. Mimicking astroglial pH-evoked Ca²⁺ responses by selective light stimulation of astrocytes expressing channelrhodopsin-2 activates chemoreceptor neurons via ATP-dependent mechanism and triggers robust respiratory and sympathetic responses in vivo. Thus, medullary astrocytes appear to be highly sensitive to physiological chemosensory challenges and have the ability to impart chemosensory information onto a modified pattern of cardiorespiratory activity. This identifies astroglia as an important brain component of one of the most fundamental mammalian homeostatic mechanisms which controls breathing and cardiovascular activity during hypercapnia and hypoxia.