Clinical observations indicate that estrogens exert a neuroprotection against neurodegenerative diseases such as Alzheimer disease. Although it is unclear whether estrogen may be effective, in preventing further cognitive decline in women who already have Alzheimer’s disease. Despite the existence somewhat controversial date from human studies experimental investigations in different animal models of neurodegenerative diseases have shown that estrogen is neuroprotective. Although estrogens are known to exert several direct effects on neurons, the cellular mechanisms involved in the neuroprotective effects of estrogen are still unclear. In this review we focus on the cellular mechanism of estrogen action in neuronal tissue.