There is increasing evidence from animal and in vitro studies to suggest that estrogen might have neuroprotective effects, and several plausible physiological mechanisms have been proposed. However, it is not yet fully understood how estrogen affects the human brain. There are several techniques that are currently employed for in vivo assessment of brain structure and function in humans, including neuropsychological and neuroendocrine testing, computerized tomography, structural and functional magnetic resonance imaging, magnetic resonance spectroscopy, single photon emission spectroscopy and positron emission tomography. Results from studies investigating the effects of estrogen on the female brain using the above techniques are reviewed here. The current data from humans suggest that the use of estrogen hormone-replacement therapy (HRT) in healthy, postmenopausal women might reduce the risk of developing Alzheimer's disease (AD) and preserve certain aspects of cognitive function. The use of HRT in postmenopausal women might also modulate neurotransmitter function and can increase cerebral blood flow in a regionally specific and task-dependent manner. In addition, the neuroprotective effects of HRT might depend on the length of its use. However, there is very little evidence at present that HRT is an effective treatment for established AD.