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Hormone replacement therapy (HRT) was initiated almost half a century ago to treat menopausal symptoms. Initially, its use remained limited even among symptomatic women and the move toward postmenopausal hormone use for disease prevention came later. Improved treatment schedules and delivery systems expanded the use of HRT worldwide. However, large trials of postmenopausal hormones with disease outcomes were even later in coming and today HRT has become a specialized, multidisciplinary area of research. As the population continues to grow older, there has been an increased focus on the effects of ageing. HRT may affect length and quality of life through disease prevention. It may have possible beneficial effects on cognition, on the incidence of hip fracture, myocardial infarction and stroke, and adverse effects on the incidence of breast cancer, endometrial cancer, and venous thromboembolism.Today’s attitudes about the hormonal treatments for the menopausal transition have moved from expansive optimism to contracting disappointment amidst safety concerns and equivocal results and faces greater skepticism and scrutiny. The health and well being of large numbers of women are at stake, and researchers, clinicians and the general public are watching and weighing the options.