Introduction: Osteoarthritis (OA) is a highly heterogenous disease influenced by different molecular, anatomic and physiologic imbalances. Some of the bottlenecks for enhanced diagnosis and therapeutic assessment are the lack of validated biomarkers and early diagnosis tools. In this narrative review, we analyze the potential of Raman spectroscopy (RS) as a label-free optical tool for the characterization of articular joint tissues and its application as a diagnosis tool for OA.Areas covered: Raman spectra produce a unique "molecular fingerprint" providing rotational and vibrational molecular information, allowing the identification and follow-up of molecular changes associated with OA pathological mechanisms. Focusing on multiple joint tissues (cartilage, synovium, bone, tendons, ligaments and meniscus) and their contribution in disease incidence and progression, this review highlights the current knowledge on the application of RS in the characterization of organic and inorganic molecules present at these tissues and alterations that occur in the onset of OA.Expert Opinion: Vibrational spectroscopy techniques, such as RS, are low cost, rapid and minimally invasive approaches that offer high specificity in the assessment of the molecular composition of complex tissues. Combined with multivariate statistical methods, RS offers great potential for optical biomarkers discovery or disease diagnosis applications, and we hereby discuss clinical translational progresses on the field.