Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that affects nearly 1 million adults in the United States. Owing to its unpredictable disease course, diverse phenotypes, and an array of currently available disease-modifying therapies, a personalized approach to MS management is required. There is an unmet need to identify, validate, and incorporate prognostic, monitoring, and predictive biomarkers into routine clinical practice for MS. A mounting body of evidence supports the use of blood biomarkers, such as neurofilament light chain (NfL), in predicting disease activity and monitoring treatment response. Previous hurdles for the widespread use of NfL in the clinical management of patients, such as invasive sampling methods and limited assay availability, are being overcome through the development and validation of new commercial serum NfL (sNfL) assays. With rising availability, there is now potential for incorporating sNfL testing to support traditional clinical assessments such as MRI, relapse rates, and disability progression measurements. However, clinical and technical limitations to the interpretation of NfL, such as comorbidities, and lack of measurement standardization and well-established reference ranges still pose challenges to its use. Based on the most recent evidence, this review aims to educate healthcare professionals on the potential utility of NfL in the clinical management of people living with MS and provide practical information on the development and availability of new assays.