- The role of zinc in neurobiology has been the subject of intense interest particularly because of zinc's presence in and release from glutamatergic synapses, and its association with major neurological disorders. Initially considered inert to Zn2+ signaling and resistant to Zn2+ toxicity, glia, like neurons, is now known to be vulnerable to Zn2+, albeit to a lesser degree and in ways that are type-specific. The discovery of Zn2+ transporters and the development of highly sensitive zinc sensors has led to a new understanding regarding the role of this metal ion in glial physiology. Dynamic changes in Zn2+ content are now linked to executive functions, signaling and fate in glia. In this review, we focus on these issues and discuss the broader implication of glial Zn2+ signaling in neuron glial-interactions. © 2012 Wiley Periodicals, Inc.