Glial cells are capable of communicating increases in [Ca2+]i from a single cell to many surrounding cells. These intercellular Ca2+ waves have been observed in glia in multiple different preparations, including dissociated brain cell cultures, glial cell lines, organotypic brain slice cultures, and intact retinal preparations. They may occur spontaneously, or in response to a variety of stimuli. Ca2+ waves occurring under different conditions in different preparations may have distinctive patterns of initiation and propagation, and distinctive pharmacological characteristics consistent with the involvement of different intracellular and intercellular signaling pathways. This paper presents original data supporting a combination of gap junction and extracellular messenger-mediated signaling in mechanically induced glial Ca2+ waves. Additional new observations provide evidence that a rapidly propagated signal may precede the glial Ca2+ wave and may mediate rapid glial-neuronal communication. This original data is discussed in the context of a review of the literature and current concepts regarding the potential mechanisms, physiological and pathological roles of this dynamic pattern of glial intercellular signaling.