Medications are approved by regulatory agencies for treating osteoporosis when at least one randomized placebo-controlled clinical trial shows a reduction in vertebral fracture risk and the benefit-risk ratio is determined to be acceptable. Subjects who participate in registration trials are a generally homogeneous group carefully screened with strict entry criteria. Individual patients who are treated for osteoporosis in clinical practice commonly differ from subjects enrolled in these clinical trials according to confounding factors that include age, sex, comorbidities, compliance, and persistence. Because the goal of therapy is reduction of fracture risk, and this cannot be directly assessed in an individual patient, biomarkers are commonly used as surrogate end points for effectiveness. This article reviews the clinical use and abuse of the two biomarkers most commonly used to assess the effectiveness of therapy in clinical practice: bone mineral density testing and measurement of markers of bone turnover.