Excessive stimulation of excitatory amino acid (EAA) receptors is responsible for a wide variety of acute and chronic neurological impairments. A separate line of investigation has focused on oxidative stress as one of the main reasons for several of these degenerative disorders. Current evidence has confirmed that activation of both ionotropic and metabotropic glutamate receptors can also result in either neuroprotection or neurodegeneration according to the role played by oxidative stress mechanisms. An outline of this research, together with our recent results aimed at the discovery of new subtype selective modulators of the central nervous system pathways as well as new classes of free radical scavengers, is presented.