From an engineering perspective, trabecular bone is a highly complex material, being anisotropic with different strengths in tension, compression, and shear and with mechanical properties that vary widely across anatomic sites, and with aging and disease. While mechanical properties depend very much on volume fraction, the role of architecture and tissue material properties remain uncertain. In the context of osteoporosis, there is wide interest in the biomechanical role of architecture since this should lead to improved understanding of the disease and ultimately better diagnosis and drug treatment assessment. This study reviews what is known about architectural changes in trabecular bone associated with age, gender and osteoporosis and the role of these changes in the mechanical properties of bone. Recent development of three-dimensional high-resolution imaging technologies has provided more accurate measures of quantitative metrics of architecture, thereby providing new data and raising questions about earlier conclusions. Focusing on the hip and spine, this literature is synthesized and outstanding issues are identified. In addition, the changing paradigm of biomechanical research on trabecular architecture is addressed. Because of the complexity of the trabecular micromechanics, the prevailing approach to date can be classified as an inverse one, whereby candidate metrics of architecture are developed and tested for efficacy in an empirical trial-and-error fashion. In this approach, the biomechanics is treated only as an assay since it is not used to guide development of the candidate metrics. By contrast, a more forward approach is to study the associated micromechanics using engineering analysis and from that identify the metrics that in theory most affect mechanical properties. The latter approach, facilitated by the new high-resolution imaging techniques and increased computational power, is discussed in an attempt to direct attention to new types of architectural metrics that are independent of bone density and that should improve the ability to explain how age, gender and osteoporosis affect the mechanical properties of trabecular bone.