Calcium (Ca2+) homeostasis is crucial for development and survival of virtually all types of cells including glia of the central nervous system (CNS). Astrocytes, oligodendrocytes and microglia, the major glial cell types in the CNS, are endowed with a rather sophisticated array of Ca2+-permeable receptors and channels, as well as store-operated channels and pumps, all of which determine Ca2+ homeostasis. In addition, glial cells detect functional activity in neighbouring neurons and respond to it by means of Ca2+ signals that can modulate synaptic interactions. Like in neurons, Ca2+ overload resulting from dysregulation of channels and pumps can be deleterious to glia. In this review, we summarize recent advances in the understanding Ca2+ homeostasis in glial cells, the consequences of its alteration in cell demise as well as in neurological and psychiatric disorders that experience glial cell loss.