In the nervous system, the concentration of Cl in neurons that express GABA receptors plays a key role in establishing whether these neurons are excitatory, mostly during early development, or inhibitory. Thus, much attention has been dedicated to understanding how neurons regulate their intracellular Cl concentration. However, regulation of the extracellular Cl concentration by other cells of the nervous system, including glia and microglia, is as important because it ultimately affects the Cl equilibrium potential across the neuronal plasma membrane. Moreover, Cl ions are transported in and out of the cell, via either passive or active transporter systems, as counter ions for K whose concentration in the extracellular environment of the nervous system is tightly regulated because it directly affects neuronal excitability. In this book chapter, we report on the Cl channel types expressed in the various types of glial cells focusing on the role they play in the function of the nervous system in health and disease. Furthermore, we describe the types of stimuli that these channels are activated by, the other solutes that they may transport, and the involvement of these channels in processes such as pH regulation and Regulatory Volume Decrease (RVD). The picture that emerges is one of the glial cells expressing a variety of Cl channels, encoded by members of different gene families, involved both in short- and long-term regulation of the nervous system function. Finally, we report data on invertebrate model organisms, such as C. elegans and Drosophila, that are revealing important and previously unsuspected functions of some of these channels in the context of living and behaving animals.