This chapter describes some of the special neurochemical features of the areas of the brain selectively vulnerable to ischemic and hypoglycemic insults. The chapter focuses on the neuronal connections to the vulnerable brain areas, on the distribution of receptors and transmitter content in the vulnerable areas, and on some current hypothesis of neuronal damage. Emphasis will be placed on a possible imbalance between excitation and inhibition of neurons as a factor in the development of neuronal necrosis, in particular the importance of excitatory transmitters, suggested to mediate ischemic and hypoglycemic brain damage. The amino acids glutamate and aspartate are major excitatory transmitters in the central neurons system. When present in high concentration they are neurotoxic and can play a role in the pathogenesis of several neurological diseases, such as temporal lobe epilepsy, Huntington's disease, and olivopontocerebellar dystrophy.