Glial cells respond to various electrical, mechanical and chemical stimuli, including neurotransmitters, neuromodulators and hormones, with an increase in [Ca²⁺]i. These glial [Ca²⁺]i signals exhibit a variety of temporal and spatial patterns. Glial [Ca²⁺]i signals can traverse gap junctions between glial cells without decrement and travel over a great distances within glial networks. The predominant source of Ca²⁺ for Ca²⁺ signal generation in astrocytes resides within the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate and ryanodine receptors of the ER provide a conduit for the release of Ca²⁺ to the cytosol. The ER store is (re)filled by the ER-specific Ca²⁺-ATPase of SERCA type. Ultimately, the depleted ER is replenished by Ca²⁺ which enters from the extracellular space to the cytosol via store-operated Ca²⁺ entry; the TRPC1 protein has been implicated in this part of the astrocytic exocytotic process. Voltage-gated Ca²⁺ channels and plasma membrane Na+/Ca²⁺ exchangers are additional means for cytosolic Ca²⁺ entry. Cytosolic Ca²⁺ levels can be modulated by mitochondria, which can take-up cytosolic Ca²⁺ via the Ca²⁺ uniporter and release Ca²⁺ into cytosol via the mitochondrial Na+ /Ca²⁺ exchanger, as well as by the formation of the mitochondrial permeability transition pore. The interplay between various Ca²⁺ sources determines cytosolic Ca²⁺ dynamics that differentially drives multiple Ca²⁺-depenent cytoplasmic processes. The highly specialised glial Ca²⁺ signals provide means for information encoding within glial networks, integrating them with neuronal circuits. An understanding of this process in vivo will reveal some of the astrocytic functions in health and disease of the brain.