Abstract: Osteoarthritis (OA) is a chronic disease with a long silent period. The hallmarks of osteoarthritis (OA) include cartilage loss that leads to joint destruction and severe impairment of mobility. Involvement of subchondral bone and synovial tissue is well documentated. OA is the most prevalent cause of disability in the aging population of developing countries.The diagnosis is generally based on clinical symptoms and radiographic changes. However, X-ray has a poor sensitivity that does not allow an early detection of OA or the monitoring of joint damage progression. Another imaging technique is the magnetic resonance imaging (MRI). Although this medical test is more sensitive than plain radiography, it is more expensive and can´t be routinely applied to many patients. The limitations offered by such tools have cleared the need to identify more specific biological markers, which evaluate quantitative variations in joint remodeling, diagnostic, prognostic and efficacy of intervention. OA affects cartilage, subchondral bone, and synovium. Thus, molecules derived from these tissues could be considered as candidates for biological markers in OA, as these molecules have a role in metabolic processes in the joints. Recent data indicates that some markers could be valuable to diagnose, predict OA progression and assess therapeutic response; however, the interpretation of results should be careful because tissue specificity, clearance rates and circadian variations are still under investigation in most of biomarkers. Although biomarkers could be considered valuable tools, they still have some limitations in clinical practice and it is necessary to develop and validate specific and sensitive biomarkers.