Postmenopausal osteoporosis is a chronic disease, which justifies long-term treatment in those women with an increased risk of fracture. The current disponibility of various drugs, which have demonstrated their efficacy in reducing the incidence of fracture, has raised the question of the best treatment strategy in a woman who would begin her postmenopausal period with an increased risk for fracture. Indeed, for most treatments (with the exception of hormonal replacement therapy [HRT]), their efficacy in reducing the risk of fracture has been mainly demonstrated in higher risk elderly women (above 65 years) with prevalent vertebral fractures. There is uncertainty concerning their cost-effectiveness in younger women for a true primary prevention of the risk of fracture. Furthermore, current guidelines recommend a 5-year period of treatment which has led us to considering treatment strategies which would be based on various sequential treatment periods over time, the selection of each specific sequence being determined by the clinical situation of the woman, the level of her fracture risk and the expected skeletal (in terms of spectrum of bone effects) and potential extraskeletal benefits of drugs. In this regard, HRT or raloxifene, which allows a more global approach of the menopause-induced consequences of estrogen deficiency than the sole prevention of osteoporosis, should be privileged within the first 10 years of treatment or so in those youngest women at increased risk for subsequent fracture. Use of bisphosphonate or strontium ranelate should be thus reserved at a more advanced age, when the prevention of hip fracture becomes mandatory.