Over the last two decades, glutamate has been established as the main excitatory neurotransmitter in the mammalian brain. Glutamate released from synapses activates ion channel-forming receptors at postsynaptic cells and consequently mediates fast postsynaptic potentials. These receptors are termed ionotropic glutamate receptors (iGluRs). The subsequent discovery of metabotropic glutamate receptors (mGluRs) revealed that glutamate can also mediate slow synaptic potentials, modulate ion channels, and directly couple to GTP binding proteins. In contrast to the iGluRs, the mGluRs possess seven transmembrane domains and a large intracellular C-terminus that involves interactions with a variety of other intracellular signaling systems. Eight functionally distinct mGluR subtypes are known to be localized to specific neuron types at presynaptic and/or postsynaptic membranes. Their physiological functions involve the generation of slow excitatory and inhibitory synaptic potentials, modulation of synaptic transmission, synaptic integration, and plasticity. The classical role of glutamate as a fast excitatory synaptic transmitter was largely extended by mGluRs acting as a neuromodulator and even as an activator of inhibitory mechanisms at certain synapses.