Hormone-replacement therapy (HRT) has been used for more than 40 years to reduce perimenopausal symptoms. Estrogens may protect brain structures and functional systems affected by Alzheimer's disease, which suggests that maintaining high levels of hormones with HRT can protect against Alzheimer's disease. Moreover, high premenopausal estrogen concentrations are thought to be protective against stroke and, consequently, in the past, HRT was considered to be a potential protective agent against stroke. However, large clinical trials have failed to demonstrate a benefit from HRT on either cognitive performance or risk of dementia. In addition, although HRT has been associated with a reduction in the risk of heart disease in observational studies, results regarding stroke have been less clear. Recently, evidence has shown that HRT does not reduce but actually increases vascular risk. Here, the data from the most important studies are examined, concluding that HRT has no beneficial effect on dementia or stroke risk reduction in postmenopausal women.