Although biomedical imaging technology is now readily available, few attempts have been made to expand the capabilities of these systems by adding not only quantitative but also functional analysis tools combining microimaging with time-lapsed mechanical testing. An area of special interest is multiscale functional imaging of trabecular bone to assess the relative importance of bone "quality" in the assessment of the mechanical competence of bone. First, relevant studies dealing with hierarchical imaging of trabecular bone and classic analyses such as quantitative morphometry and finite-element analysis to predict bone strength are reviewed. Second, studies are presented investigating failure mechanisms of three-dimensional trabecular bone through dynamic, time-lapsed microimaging, including image-guided techniques developed for this purpose and utilizing microcompression. For the first time, these allow the direct three-dimensional visualization and quantification of failure initiation and progression at the microstructural level.