The strength of trabecular bone and its resistance to fracture traditionally have been associated with apparent density. This paradigm assumes that neither the ultrastructural nor microstructural make-up of the bone is altered during aging and osteoporosis. During the past decade there has been growing evidence from both laboratory and clinical studies against this view. Recent advances in noninvasive imaging technology, notably micro-magnetic resonance imaging (μ MRI) and computed tomography, offer an opportunity to test the hypothesis that architecture is an independent contributor to bone strength. MRI appears to be ideally suited for this task because bone marrow has uniform high signal intensity while bone appears with background intensity, thus yielding a binary system tomographic system. However, in vivo trabecular bone imaging is hampered by the limited signal-to-noise ratio that precludes voxel sizes much smaller than trabecular thickness, which would be required to yield a bimodal intensity histogram for segmentation of the image into bone and marrow. The resulting partial volume blurring leads to fuzzy boundaries. Successful structure analysis thus demands more elaborate processing strategies. This article reviews new approaches conceived in the authors' laboratory toward acquisition, processing, and structural analysis of trabecular bone images in the limited spatial resolution regimen of in vivo μ MRI. These methods are shown to provide detailed insight into the three-dimensional trabecular network topology and scale at the distal radius or distal tibia that typically serve as surrogate sites. The μ MRI–derived structural parameters are shown to be associated with the bone's biomechanical properties and fracture resistance. Further, the technology has advanced to a stage permitting serial studies in laboratory animals and humans as a means to evaluate the effects of treatment. The method currently is confined to peripheral skeletal sites, and its extension to typical fracture sites such as the proximal femur hinges on further advances in detection sensitivity.