The aim of this narrative review is to summarize important findings from biochemical marker studies relevant to osteoarthritis (OA) in the context of new discoveries and clinical and scientific need. Design: We conducted a systematic search of electronic medical databases (Embase, Medline, Web of Science, Cochrane central) between 01-03-2017 and 31-03-2018. The search was restricted to human studies, English language and full text available publications while reviews were excluded. Only papers describing protein based biomarkers measured in human body fluids (blood, urine and synovial fluid (SF)) were included. Of the 992 papers, 86 were reviewed here, with inclusion primarily based on relevance to OA biochemical markers. Results: This review highlights a selection of studies based on their quality and perceived importance to the field mainly including those that 1 evaluate prognostic value of biomarkers for OA progression (i.e., biomarkers reflecting change in composition of joint tissues and biomarkers of inflammation) 2 , help in assessment of intervention efficacy, and 3 are innovative and uncover new candidate biomarkers, or use new approaches in biomarker discovery. Conclusions: Key findings and implications for possible clinical utility of biochemical markers are summarized and discussed. Given the paucity of robust biomarkers within the field, and the heterogeneity of the condition, enormous works are needed for development and validation of novel and clinically applicable biomarkers to reduce the impact of this highly prevalent and debilitating condition.