Inhibition at central synapses is majorly mediated by glycine and γ-aminobutyric acid (GABA). Glycine acts by binding to a specific receptor and opening an intrinsic chloride channel. The inhibitory glycine receptor (GlyR) widely expressed in many regions of the central nervous system is a member of the ligand-gated ion channel receptor superfamily. GlyR consists of five similar subunits (3α, 2β) arranged to form a ring around a central pore. Since the glycine-binding site is distant from the pore, long-range allosteric interactions are needed to couple agonist binding to channel gating. Recent advances in understanding the structure, physiological and pharmacological characteristics of GlyR are reviewed and modulation of GlyR and possible underlying mechanisms are discussed, in special reference to the recent work in our laboratory.