Biomarkers of skeletal turnover, such as the synthesis and degradation of extracellular matrix molecules in specific tissues, offer the opportunity to gain new insights into spinal pathology and treatment. The creation, use, and interpretation of these analytical body-fluid measures of process (rather than outcome) require a clear understanding of the nature of the molecules and events being measured. This review provides examples of how protein and carbohydrate assays of biomarkers can be used to measure the contribution from the intervertebral discs and vertebrae of the spine. With regard to spinal degeneration and ankylosing spondylitis, these investigations are providing important new information, in weeks rather than years, on the response of patients to treatment.