© 2014 Springer Science+Business Media New York. All rights reserved. Excitability of astrocytes is based on spatio-temporally organized fluctuations of intracellular concentrations of two ions, Ca2+ and Na+. This is dictated by ionic movements between intracellular compartments, and between the cytosol and the extracellular space, achieved by concentration-driven diffusion through membrane channels or transport by pumps and exchangers. Neuronal activity triggers transient elevation of Ca2+ and Na+ in astrocytes; changes in cytosolic levels of these ions translate into functional responses through multiple molecular cascades. Aberrant ionic signaling contributes to pathological reactions of astroglia in various forms of neurological diseases, such as stroke, epilepsy, and various neurodegenerative and neuropsychiatric disorders.