Estradiol, in addition to its participation in neuroendocrine regulation and sexual behavior, has neuroprotective properties. Different types of brain injury induce the expression of the enzyme aromatase in reactive astroglia. This enzyme catalyzes the conversion of testosterone and other C19 steroids to estradiol. Genetic or pharmacological inhibition of brain aromatase results in marked neurodegeneration after different forms of mild neurodegenerative stimuli that do not compromise neuronal survival under control conditions. Furthermore, aromatase mediates neuroprotective effects of precursors of estradiol such as pregnenolone, dehydroepiandrosterone (DHEA) and testosterone. These findings strongly suggest that local formation of estradiol in the brain is neuroprotective and that the induction of aromatase and the consecutive increase in the local production of estradiol are part of the program triggered by the neural tissue to cope with neurodegenerative insults. Aromatase may thus represent an important pharmacological target for therapies conducted to prevent aging-associated neurodegenerative disorders.