The adenosine 5'-triphosphate (ATP), discovered in 1929 by Karl Lohman, Cyrus Hartwell Fiske, and Yellagaprada SubbaRow, acts as an important extracellular signaling molecule. In the CNS, ATP can be released from synaptic terminals, either on its own or together with other neurotransmitters. After the release from the presynaptic terminals, ATP binds to a plethora of ionotropic and metabotropic receptors, which mediate its action as an excitatory neurotransmitter. Furthermore, ATP also acts as an important mediator in neuronal-glial communications because glial cells are endowed with numerous ATP receptors, which trigger Ca(2+) signaling events and membrane currents in both macro and microglia. In addition, ATP can be released from astroglial cells, thereby acting as a mediator of glial-glial and glial-neuronal signaling.