Extracellular ATP is both a transmitter and a signalling molecule in the CNS. During various types of brain damage (e.g. mechanical or ischemic injury) large quantities of ATP enter the extracellular space and activate ionotropic P2X and metabotropic P2Y receptor-types situated at both neurons and glial cells. The stimulation of P2X receptors causes depolarization and the excessive entry of Ca2+ leading to apoptosis and necrosis. P2Y receptors mostly initiate proliferative changes in astrocytes. A special subtype of the P2X receptor, named P2X7 has been originally described to occur in peripheral immunocytes such as macrophages and lymphocytes. However, central immunocytes (astrocytes, microglia, Muller cells of the retina) also appear to be endowed with P2X7 receptors. More recently the existence of neuronal P2X7 receptors has been proposed based both on immunohistochemistry and functional studies. However, a major debate has emerged on the selectivity of the antibodies used to recognize central P2X7 receptors. Based on pharmacological experiments we suggest that such receptors are present and become hypersensitive in primary cultures of cerebrocortical neurons following short-term in vitro ischemia (hypoxia and glucose-deficiency). Similarly, previously absent P2X7-immunoreactivity became apparent on both neurons and astrocytes in the peri-infarct region after medial cerebral artery occlusion of rats.