In recent years our appreciation that estradiol is truly a pleiotropic hormone has grown dramatically. We will review the findings that suggest that estrogens may exert important non-reproductive actions on the brain. These studies provide important insights into the clinical effects of estrogen replacement therapy on age- and disease-related processes in the brain. We will also discuss the multiple cellular and molecular mechanisms that may underlie estradiol's neurotrophic and neuroprotective effects.