The glutamate transmitter system provides several benevolent/malevolent paradoxes. Glutamate itself serves vitally important functions in the CNS but has enormous neurodestructive potential. NMDA glutamate receptor antagonists protect many neurons against glutamate neurotoxicity, while injuring or destroying certain other neurons and inducing psychotic symptoms and memory impairment. Therefore, the challenge in developing protective therapies against glutamate's neurodestructive potential is to find benevolent agents that are not malevolent as well. There are two possible approaches. One is to develop neuroprotective agents that are free from neuropsychopathological side effects; the other is to use NMDA antagonists even though they have neuropsychopathological side effects, but to use them in combination with other agents that block the side effects without producing side effects of their own.