In addition to providing structural, metabolic and trophic support to neurons, glial cells of the central, peripheral and enteric nervous systems (CNS, PNS, ENS) respond to and regulate neural activity. One of the most well characterized features of this response is an increase of intracellular calcium. Astrocytes at synapses of the CNS, oligodendrocytes along axons of the CNS, enteric glia associated with the cell bodies and axonal varicosities of the ENS, and Schwann cells at the neuromuscular junction (NMJ) and along peripheral nerves of the PNS, all exhibit this response. Recent technical advances have facilitated the imaging of neural activity-dependent calcium responses in large populations of glial cells and thus provided a new tool to evaluate the physiological significance of these responses. This mini-review summarizes the mechanisms and functional role of activity-induced calcium signaling within Schwann cells, including terminal/perisynaptic Schwann cells (TPSCs) at the NMJ and axonal Schwann cells (ASCs) within peripheral nerves.