For decades, estrogens have been regarded as reproductive hormones. However, research in the last few years has altered this perspective. It has been shown that estrogen signaling plays a widespread and crucial role in regulating brain function throughout life in both men and women. This review summarizes recent studies from 2005 to 2025 on how estrogens work in the brain, including their mechanisms, targets, and effects. We outline where nuclear estrogen receptors (ERα, ERβ) and membrane-associated receptors (like GPER1) are found in the brain. We also highlight their roles in synaptic plasticity, adult neurogenesis, inflammation and energy use. We examine the protective and cognitive benefits of estrogens, particularly regarding neurodegenerative diseases like Alzheimer’s, psychiatric issues such as depression, and brain injuries. We emphasize the importance of timing, dosage, and hormonal context within the "window of opportunity" or "critical period" hypothesis. Recent updates to hormone replacement therapy (HRT) guidelines highlight the brain health benefits of starting treatment early.