Over the last decades estrogen has been recognized to be involved in normal brain function due to its neurothrophic and neuroprotective effects. Estrogen is intimately associated with neuronal survival, mitochondrial function, neuroinflammation and cognition through genomic as well as non-genomic pathways. It is also known that the neuroprotective actions mediated by estrogens are interlinked with the insulin-like growth factor-1 (IGF-1) signaling pathway. This review is mainly devoted to explore the physiological and pathophysiological effects of estrogen and its signaling pathways in the brain. The molecular mechanisms underlying these effects are also debated. Finally, we discuss the potential neuroprotection afforded by estrogens in Alzheimer's disease pathophysiology focusing in the "window of opportunity" for the initiation of estrogen therapy as a critical factor in the fight against neurodegeneration.