Activation of ionotropic receptors by glutamate mediates most of the fast excitatory synaptic transmission in mammalian central nervous system. In addition, they are involved in excitotoxic neuronal cell death that occurs in a variety of neurological disorders if these receptors are excessively activated. Metabotropic glutamate receptors (mGluRs) are a G-protein coupled receptor family and they are divided into three groups. Both group II and group III of mGluRs are presynaptically localized on the glutamatergic terminals, and provide a negative feedback to modulate the release of glutamate. Recent data also showed that some mGluRs are presented on non-glutamatergic neurons, such as GABAergic terminals, where mGluRs suppress GABA release when they are activated. Further investigation of mGluRs may lead to the development of novel, safe and effective pharmacological agents to treat a range of neurological disorders and neurodegenerative diseases by preventing the excessive glutamate release.