The determinants of charge selectivity of the Cys-loop family of ligand-gated ion channels have been studied for more than a decade. The investigations have mainly covered homomeric receptors e.g. the nicotinic acetylcholine receptor alpha7, the glycine receptor alpha1 and the serotonin receptor 5-HT(3A). Only recently, the determinants of charge selectivity of heteromeric receptors have been addressed for the GABA(A) receptor alpha2beta3gamma2. For all receptor subtypes, the selectivity determinants have been located to an intracellular linker between transmembrane domains M1 and M2. Two features of the M1-M2 linker appear to control ion selectivity. A central role for charged amino acid residues in selectivity has been almost universally observed. Furthermore, recent studies point to an important role of the size of the narrowest constriction in the pore. In the present review, these determinants of charge selectivity of the Cys-loop family of ligand-gated ion channels will be discussed in detail.