Our knowledge of glycine receptor (GlyR) regulation of excitation has advanced significantly in recent years. GlyRs are widespread in the CNS, are heterogeneous, and undergo developmental changes. Activation of GlyRs of immature neurons induces outflow of Cl( - ), membrane depolarization, neuronal excitation, calcium influx, and transmitter release, in contrast to the inhibitory effects these receptors have in mature neurons. Thus, GlyRs are important for neuronal excitability in both the developing and the mature CNS. This chapter is an overview of selective studies on the newly discovered roles of GlyRs in regulating neuronal excitation, and inhibition, particularly in the upper brain areas.