Glutamic acid is an essential participant of brain metabolism. It is known that the glutamate is a neurotransmitter in a numerous part of the brain synapses and acts through various ionotropic or metabotropic receptors. Multiple alterations of the brain glutamate system are observed in both acute and chronic brain injures. Glutamate metabolism changes take place in many neurodegenerative pathologies, such as brain ischemia, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis etc. These disruptions may be related to changes of glutamate metabolism enzyme activities, alterations of the main energy formation reactions in mitochondria, and shifts of oxidation/redox balance in cells. Potential targets for therapy of neurodegenerative diseases, especially in chronic treatment, can include the drugs for recovery of glutamate metabolism system.