Molecular cloning of ionotropic glutamate receptors and the development of new measurement techniques have significantly advanced our understanding of the molecular mechanisms controlling ligand-mediated entry of Ca2+ into neurons of the mammalian CNS. Recent studies have demonstrated that various types of glutamate receptors expressed in different nerve cells are permeable to Ca2+ to variable extents, depending on the structural peculiarities of the subunits and their composition in a particular cell. This diversity provides a regulable pathway for Ca2+ entry during synaptic transmission. The fractional contribution of this Ca2+ to the total synaptic current might be a substantial means of elevating the intracellular Ca2+ concentration over a wide temporal range.