The estradiol transdermal therapeutic system is a percutaneous delivery device which, when affixed to the skin, delivers estradiol (the major estrogen in premenopausal women) into the systemic circulation at a constant rate for up to 4 days. Because this method of delivery avoids first-pass hepatic metabolism, premenopausal levels of estradiol can be maintained in postmenopausal women using very low dosages. Bone density decreases at an accelerated rate after the menopause, which can lead to development of osteoporosis and increased fracture risk. In common with other estrogen therapies, transdermal estradiol provides protection against osteoporosis following spontaneous or surgical menopause, as evidenced by both biochemical markers of bone resorption and, in a small number of studies, measurement of bone mineral density. Protection against further vertebral fractures was also demonstrated in women with established osteoporosis in one study. Transdermal estradiol also has beneficial effects on vaginal cytology and menopausal symptoms similar to those of oral estrogens. The tolerability of transdermal estradiol appears to be very good, the most common adverse effect being local irritation at the application site. As with other estrogens, transdermal estradiol can be given continuously or in 4-week (3 weeks on/1 week off) cycles, and concomitant progestogen therapy is recommended in women with intact uteri, in order to minimise the risk of endometrial hyperplasia. Available evidence thus suggests that transdermal estradiol may represent an attractive alternative to other forms of estrogen therapy for the prevention, and possibly treatment, of postmenopausal osteoporosis.