Fracture prevention is the goal of osteoporosis treatment. Bone mineral density (BMD) has been the main criterion for deciding whether to initiate treatment, which is usually recommended when the BMD is less than -2.5 SDs from the mean in young women. However, the need to base treatment decisions on the overall fracture risk, rather than on BMD values alone, is now increasingly recognized. Several factors predict the fracture risk independently from BMD. Combining these factors to BMD may improve patient selection for osteoporosis therapy. In addition to low BMD values, factors associated with a high fracture risk include advanced age, prior fractures in the patient or family, low body mass index, smoking, glucocorticoid therapy, unfavorable profile of bone turnover markers, and risk factors for falls. There is no consensus yet about the best strategy for using these risk factors to assist in treatment decisions. A collaborative center set up by the World Health Organization is evaluating pooled data from prospective studies in order to better define high-risk patient subsets that are likely to benefit from osteoporosis treatment to prevent fractures. The results will serve to develop clinical guidelines for identifying high-risk patients.