Neurofilament proteins, particularly neurofilament light (NfL), are promising biomarkers for neuroaxonal damage in various neurological disorders. These proteins rise in cerebrospinal fluid (CSF) and blood following neuroaxonal damage, reflecting neuronal injury independent of causal pathways. Early-generation assays were limited in sensitivity, but third-generation electrochemiluminescence and fourth-generation single molecule array assays have significantly improved detection capabilities, enabling reliable measurement of NfL levels in blood samples across a wide range of concentrations. This advancement has facilitated the investigation of NfL in multiple neurological disorders, including multiple sclerosis, neurodegenerative dementias, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and Parkinson's disease. Studies have shown that NfL levels correlate with disease activity, disability, and treatment responses, making it a valuable tool for monitoring disease progression and therapeutic efficacy. However, further research is needed to establish universal reference values and understand the mechanisms underlying age-related changes in NfL levels. Overall, highly sensitive neurofilament measurements have the potential to enhance the assessment of neuroaxonal damage and guide clinical decision-making in neurological disorders.Neurofilament proteins, particularly neurofilament light (NfL), are promising biomarkers for neuroaxonal damage in various neurological disorders. These proteins rise in cerebrospinal fluid (CSF) and blood following neuroaxonal damage, reflecting neuronal injury independent of causal pathways. Early-generation assays were limited in sensitivity, but third-generation electrochemiluminescence and fourth-generation single molecule array assays have significantly improved detection capabilities, enabling reliable measurement of NfL levels in blood samples across a wide range of concentrations. This advancement has facilitated the investigation of NfL in multiple neurological disorders, including multiple sclerosis, neurodegenerative dementias, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and Parkinson's disease. Studies have shown that NfL levels correlate with disease activity, disability, and treatment responses, making it a valuable tool for monitoring disease progression and therapeutic efficacy. However, further research is needed to establish universal reference values and understand the mechanisms underlying age-related changes in NfL levels. Overall, highly sensitive neurofilament measurements have the potential to enhance the assessment of neuroaxonal damage and guide clinical decision-making in neurological disorders.