Hormone replacement therapy (HRT) is effective for relieving vasomotor symptoms such as hot flash and vaginal atrophy and for preventing bone loss in postmenopausal and bilaterally ovariectomized women. However, compliance with HRT was reported to be low despite the benefits of HRT. In addition, results of several recent large-scale randomized clinical trials have demonstrated that protection from cardiovascular disease is not an indication for treatment with estrogen and progestin in postmenopausal women. Recent studies have demonstrated that low-dose HRT is safe and effective for prevention of postmenopausal bone loss. Low-dose HRT has also been shown to be effective for reducing the number and severity of hot flashes, improving vaginal atrophy, and inducing favorable changes in lipids, lipoproteins and hemostatic factors. Moreover, low-dose regimens of CEE (conjugated equine estrogen) and MPA (medroxyprogesterone acetate) result in higher rates of amenorrhea and endometrial protection compared with the conventional dose of HRT. Low-dose HRT may improve the compliance rate and may be more effective than conventional-dose HRT for reducing the risk of breast cancer. On the other hand, it has been shown that transdermal estrogen treatment reduces the incidence and severity of hot flashes and that long-term treatment with transdermally administered estrogen is effective for protection against osteoporosis. Transdermal administration of estrogen is recommended in postmenopausal women with hypertriglycemia because this treatment has little effect on lipid metabolism. The serum estradiol level was reported to be closely related to estrogenic effects on various tissues. An HRT regimen should be based on the needs of each patient. Serum estradiol levels in women should be maintained at appropriate levels for benefits and not be excessively high in order to prevent side effects. Selection of the most appropriate regimen of HRT (dose, route of administration and schedule) for the needs of the individual are important factors to increase the rate of continuation with HRT.