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Although it has been more than 20 years since the first recorded use of a quantitative ultrasound (QUS) technology to predict bone fragility, the field has not yet reached its maturity. QUS has the potential to predict fracture risk in several clinical circumstances and has the advantages of being nonionizing, inexpensive, portable, highly acceptable to patients, and repeatable. However, the wide dissemination of QUS in clinical practice is still limited and suffering from the absence of clinical consensus on how to integrate QUS technologies in bone densitometry armamentarium. Several critical issues need to be addressed to develop the role of QUS within rheumatology. These include issues of technologies adapted to measure the central skeleton, data acquisition, and signal processing procedures to reveal bone properties beyond bone mineral quantity and elucidation of the complex interaction between ultrasound and bone structure. This article reviews the state-of-the-art in technological developments applied to assess bone strength in vivo. We describe generic measurement and signal processing methods implemented in clinical ultrasound devices, the devices and their practical use, and performance measures. The article also points out the present limitations, especially those related to the absence of standardization, and the lack of comprehensive theoretical models. We conclude with suggestions of future lines and trends in technology challenges and research areas such as new acquisition modes,, advanced signal processing techniques, and modelization.