It is possible to use biomarkers in cohort studies and in clinical trials to increase our understanding of disease, to elucidate disease mechanisms, and to bolster a clinical impression of the disease state of osteoarthritis. Whether it will be possible to utilize biomarkers meaningfully to characterize the disease state in an individual patient remains to be seen. Major concepts related to the use of biomarkers for research and clinical practice, and factors influencing biomarker concentrations, are described in this review in order to address the potential role of biomarkers in osteoarthritis diagnosis, prognosis, and treatment.