<p>Alzheimer’s Disease (AD) prevalence and lifetime risk are higher in women than men. This led to the hypothesis that menopause, with its associated changes in female hormone homoeostasis, may be an AD risk factor modifiable by hormone replacement therapy (HRT). However, HRT is not without its risks to women’s health, and any recommendations must rest on sound evidence. Here, we critically review data concerning sex-specific epidemiological and biological parameters that may influence AD development. Recent epidemiological studies suggest that the age-adjusted incidence of AD is not higher in women than men. Whilst there is mechanistic experimental evidence that female sex hormones modulate the metabolism of β-amyloid and tau, the neuropathological hallmarks of AD, no clear conclusions can be drawn from studies conducted in humans. Exposure to HRT may modify the development of AD; however, data are weak and the influence of timing, duration, type of HRT, and ethnic, socioeconomic, educational and genomic factors such as <i>APOE</i> genotype, requires further clarification. Large prospective biobank studies in diverse populations, with long follow-up periods and application of biological consensus criteria for the diagnosis of AD provide opportunities to conclusively clarify the relationship between menopause, HRT therapy and risk for the development of AD. Based on current evidence, HRT cannot be recommended as a generic intervention for the reduction of AD risk in women. Any decision to take HRT must consider the individual circumstances and overall health of a woman.</p>