Metabotropic glutamate (mGlu) receptors are a large, heterogeneous family of G-protein coupled receptors, which modulate excitatory synaptic transmission through various transduction pathways. Evidence is now accumulating that individual mGlu-receptor subtypes mediate distinct, facilitatory (group I subtypes) or inhibitory (group II and group III subtypes), actions on neurodegenerative processes. Drugs interacting with mGlu receptors are expected to influence both the induction and progression of neuronal degeneration without hampering the efficiency of fast excitatory synaptic transmission. For these reasons, mGlu receptors can be considered as promising drug targets in the experimental therapy of acute or chronic neurodegenerative diseases.