Ligand-gated channels activated by excitatory neurotransmitters: glutamate, acetylcholine, ATP or serotonin are cation channels permeable to Ca2+. Molecular cloning revealed a large variety of the ligand-gated channel subunits differentially expressed in mammalian brain. Many of them have different Ca2+ permeability providing immense diversity in Ca2+ entry mediated by ligand-gated channels during synaptic transmission. Functional analysis of cloned channels allowed to identify structural elements in the pore forming regions determining Ca2+ permeability for many types of ligand-gated channels. The functional role of the Ca2+ entry mediated by various ligand-gated channels in mammalian central nervous system is less understood. The studies reviewed in this article provide information about known structural determinants of Ca2+ permeability of the ligand-gated channels and the role of this particular pathway of Ca2+ entry in cell function.