The purpose of this overview of osteoarthritis (OA) biomarkers is to provide the non-specialist with a toolbox, based on experience acquired by biomarker researchers over many years, to understand biomarkers in general and their use in the OA field. We provide an update on this subject since the OARSI Primer on osteoarthritis (OA) nearly a decade ago. Since the last update, the importance of molecular biomarkers has been increasingly recognized in the field, but no OA-related biomarkers have been adopted for routine use in clinical practice. The current lack of chondroprotective treatments for OA impairs the assessment, validation and qualification of the potential role of biomarkers as tools for monitoring disease status and patient responses to treatment of OA. Yet there is no lack of an evolving compendium of OA-related biomarkers, ever more fit-for-purpose, that could currently facilitate drug development for OA. We provide an abbreviated update and overview of specific soluble OA-related biomarkers for this new OARSI Primer on OA with OA-relevant examples encompassing the concepts of biomarker nomenclature, qualification, interpretation, measurement, reporting requirements, application to research, drug discovery and clinical care, and future needs for biomarker advancement. Appropriate biomarkers should play a role at all stages of OA diagnosis, prognosis, drug development, and treatment. The future of OA biomarker research and development holds great promise as its foundation is increasingly robust.