Serum neurofilament light chain (sNfL), a neuronal structural protein, is released upon neuroaxonal damage and correlates with clinical and imaging activity, brain atrophy, and disability progression, though it is not disease-specific. This review addresses measurement methods (SiMoA, automated platforms), pre-analytics/matrix effects, and central confounders (esp. age, BMI/volume of distribution, renal function, intercurrent events), emphasizing standardization via age- and BMI-corrected reference data using Z-scores or percentiles.Clinically, sNfL supports baseline risk stratification and treatment planning, serial treatment monitoring as an early warning signal for subclinical disease activity, the differentiation of relapse versus pseudo-relapse, the assessment of progressive courses, and decision-making in special situations (pregnancy, older age, de-escalation). Serial measurements are superior to single measurements for longitudinal assessment. Priorities include assay harmonization and prospective studies on NfL-guided, multimodal decision strategies.