Osteoporosis is one of the main features of the ageing process and the cost of health care for osteoporosis-related fractures and their complications is a major incentive for prevention, particularly in developed countries with a continuously ageing population. The earliest strategies for prevention in menopaused women were based on the anti-osteoclastic effect of hormone replacement therapy. Several epidemiological studies have provided proof of its efficacy showing that in treated populations, there is a significant reduction in osteoporosis-related fractures of about 50%, whatever the site of fracture. Although the effects of hormone replacement therapy in the prevention of post-menopausal osteoporosis have been well established, three problems remain. First, what is the degree of efficacy if replacement therapy is started late? Second, what is the effect in patients who have already suffered an osteoporotic fracture? Third, and most importantly, what is the optimal duration of treatment for effective prevention in a given population particularly at risk of hip fracture? These questions suggest new strategies for preventive hormone replacement are needed.