Although rarely used to diagnose and manage patients with osteoporosis, bone biopsies are performed to establish bone quality, including degree of mineralization and microarchitecture; to assess bone turnover and bone loss mechanisms; and to analyze treatment effects on bone structure and bone turnover. Bone biopsies are also the only method to diagnose mineralization defect or frank osteomalacia. Due to the availability of antiresorptive agents and anabolic drugs, determining bone turnover and bone-loss mechanisms is critical to appropriate treatment regimen selection. Bone biopsies establish the safety and efficacy of new therapeutic modalities. Further, new techniques such as molecular morphometry (in situ hybridization and immunohistochemistry) and analysis of bone content and crystal perfection have been applied to undecalcified bone and elucidated pathogenetic mechanisms or abnormalities in bone microstructure.