Several lines of evidence indicate that the elaborated calcium signals and the occurrence of calcium waves in astrocytes provide these cells with a specific form of excitability. The identification of the cellular and molecular steps involved in the triggering and transmission of Ca2+ waves between astrocytes resulted in the identification of two pathways mediating this form of intercellular communication. One of them involves the direct communication between the cytosols of two adjoining cells through gap junction channels, while the other depends upon the release of “gliotransmitters” that activates membrane receptors on neighboring cells. In this review we summarize evidence in favor of these two mechanisms of Ca2+ wave transmission and we discuss that they may not be mutually exclusive, but are likely to work in conjunction to coordinate the activity of a group of cells. To address a key question regarding the functional consequences following the passage of a Ca2+ wave, we list, in this review, some of the potential intracellular targets of these Ca2+ transients in astrocytes, and discuss the functional consequences of the activation of these targets for the interactions that astrocytes maintain with themselves and with other cellular partners, including those at the glial/vasculature interface and at perisynaptic sites where astrocytic processes tightly interact with neurons. © 2006 Wiley-Liss, Inc.