PURPOSE OF REVIEW: We provide a critical review of recent in-vitro, animal and human clinical studies on type II collagen biomarkers. In describing the human studies, we have applied the BIPED (burden of disease, investigative, prognostic, efficacy of intervention, and diagnostic) classification scheme recently proposed by the Osteoarthritis Biomarkers Network (a consortium of five US National Institutes of Health designated sites). Based on this analysis, we propose an update to the classification of the type II collagen biomarkers. RECENT FINDINGS: Various type II collagen epitopes have been described as potential biomarkers for osteoarthritis. Some have demonstrated ability in the following areas: classification of individuals as either diseased or nondiseased; assessment of severity or extent of osteoarthritis; prediction of future onset of osteoarthritis among those without osteoarthritis at baseline or the progression of osteoarthritis among those with existing disease; and monitoring treatment efficacy. SUMMARY: Type II collagen biomarkers provide useful information for clinical and research applications. Furthermore, they are promising tools for the monitoring the influence of drug treatment on cartilage metabolism in joint diseases such as osteoarthritis.