This review summarizes current knowledge relating intracellular calcium and glial function. During steady state, glia maintain a low cytosolic calcium level by pumping calcium into intracellular stores and by extruding calcium across the plasma membrane. Glial Ca2+ increases in response to a variety of physiological stimuli. Some stimuli open membrane calcium channels, others release calcium from intracellular stores, and some do both. The temporal and spatial complexity of glial cytosolic calcium changes suggest that these responses may form the basis of an intracellular or intercellular signaling system. Cytosolic calcium rises effect changes in glial structure and function through protein kinases, phospholipases, and direct interaction with lipid and protein constituents. Ultimately, calcium signaling influence glial gene expression, development, metabolism, and regulation of the extracellular milieu. Disturbances in glial calcium homeostasis may have a role in certain pathological conditions. The discovery of complex calcium-based glial signaling systems, capable of sensing and influencing neural activity, suggest a more integrated neuro-glial model of information processing in the central nervous system.