Glutamate is the main excitatory neurotransmitter in the brain. For many years it has been considered to act only on ligand-gated receptor channels—termed NMDA, AMPA and kainate receptors—involved in the fast excitatory synaptic transmission. Recently, glutamate has been shown to regulate ion channels and enzymes producing second messengers via specific receptors coupled to G-proteins. The existence of these receptors, called metabotropic glutamate receptors, is changing our views on the functioning of fast excitatory synapses.