Transilial bone biopsy after tetracycline labeling coupled with histomorphometry has become an indispensable tool in the clinical research of metabolic bone disease, especially in evaluating the long-term safety and efficacy of therapeutic agents proposed for treatment of bone disease. It is probably not necessary for the majority of patients who seek medical care for bone diseases such as osteoporosis. It is particularly useful in the management of patients with end-stage renal disease who develop symptomatic bone disease because it may be the only means of deciding on proper treatment. The biopsy can be performed safely by nearly any clinician after brief training. Tetracycline labeling must be accomplished before the biopsy, and the specimen must be handled carefully to avoid removal of the mineral or disturbing the label. Embedding, sectioning, staining, and analysis must be performed without removal of the mineral. The difficulty of this methodology has limited its availability. Nevertheless, it can be applied in most situations in which there is clear benefit to patient management.