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The diagnostic utility of biomarkers in multiple sclerosis (MS), particularly kappa free light chains (kFLC) in cerebrospinal fluid (CSF), has been explored for over four decades. Recent advancements have led to the incorporation of kFLC as a surrogate marker for oligoclonal bands in the latest revision of the McDonald criteria, facilitating earlier and more streamlined diagnosis in clinical practice. Additionally, emerging biomarkers such as neurofilament light chains (NfL) and glial fibrillary acidic protein (GFAP) are gaining increasing attention in neurological research and will also be discussed.