Osteoarthritis (OA) is a chronic joint disorder characterized by articular cartilage destruction, subchondral bone alteration and variable synovial inflammation. Diagnosis of the disease, the progression of joint damage, and the monitoring of effect of structure modifying treatment, are still based on less sensitive evaluation of clinical and radiological findings. Molecular markers represent a new field of interest to serve as surrogate indicators for OA evaluation. These markers may provide direct information about the alteration of joint tissue metabolism and related bone and cartilage turnover and/or local inflammation. Currently available molecular markers or their combinations may provide a tool for early onset detection of OA. Additionally, these markers may aid in the identification of patients at high risk of rapid joint destruction, and the prediction of OA progression. Molecular markers may also play a very important role in the monitoring of the responsiveness to OA treatment.