Quantitative ultrasound (QUS) techniques have found widespread clinical use, but their specific role in clinical practice needs further refinement. This review discusses the ability of QUS approaches to predict the risk for prevalent vertebral fractures and the risk for future fractures. QUS approaches perform as well as central dual x-ray absorptiometry devices but with some disadvantages (at least for older QUS approaches) with regard to the predictive power for hip fractures. Technologic diversity of QUS approaches may lead to differences in performance. QUS also has the potential for assessing bone mineral density-independent aspects of bone composition that are relevant for bone strength. For measurements at the calcaneus, it is evident that bone microstructure is the key determinant of QUS variables obtained. However, in most cases, microstructure is so highly correlated with bone mineral density that no separate assessment can be performed in clinical practice. At cortical sites, a selective assessment of bone properties is easier. Technologies need to be adapted to this purpose because requirements differ significantly from those desired for optimum fracture risk assessment. More importantly, multiple partially independent QUS variables need to be defined to assess complementary aspects of bone tissue.