Osteoporosis is a multifactorial disorder of bone mineral homeostasis affecting the elderly. It is a major public health issue with significant socioeconomic consequences. Recent findings suggest that bone loss—the key manifestation of the disease—is accompanied by architectural deterioration, both affecting the bone's mechanical competence and susceptibility to fracture. This article reviews the potential of quantitative micro MRI (μ-MRI), including a discussion of the technical requirements for image acquisition, processing, and analysis for assessing the architectural implications of osteoporosis and as a means to monitor the response to treatment. With current technology, the resolution achievable in clinically acceptable scan times and necessary signal-to-noise ratio (SNR) is comparable to trabecular thickness. This limited spatial resolution regime demands processing and analysis algorithms designed to operate under such limiting conditions. It is shown that three different classes of structural parameters can be distinguished, characterizing scale, topology, and orientation. There is considerable evidence that osteoporotic bone loss affects all three classes but that topological changes, resulting from conversion of trabecular plates to rods, with the latter's eventual disconnection, are particularly prominent. Clinical applications discussed can be divided into those dealing with assessment of osteoporotic fracture risk as opposed to the study of the effect of disease progression and regression in response to treatment. Current data suggest that noninvasive assessment of cortical and trabecular bone (TB) architecture by μ-MRI may provide new surrogate endpoints to assess the efficacy of intervention in osteoporosis treatment and prevention.