Highly sensitive immunoassays for the detection of neuro-specific biomarkers are becoming more accessible. Currently, the majority of these biomarkers are detected with the use of labour-intensive and highly skilled wet lab work. However, recent advancements have allowed for the introduction of these neuro-specific biomarkers into mainstream clinical chemistry analysers, bringing them closer to clinical care. There is a vast amount of published literature for neuro-specific biomarkers in an adult and ageing population, unfortunately, the same cannot be said for the neonatal population. From the limited available literature, clear differences are being documented in physiological levels of neuro-specific biomarkers in adults and infants. Neuro-specific biomarkers such as GFAP (Glial Fibrillary Acidic Protein) and Tau are demonstrating promise for the early detection and prediction of neuro-developmental disorders. There is a need for an understanding of physiological levels of these neuro-specific biomarkers in a neonatal population before they can be fully adopted into clinical routine. The development of a neonatal reference interval for neuro-specific biomarkers may provide a foundation for the accurate interpretation of neuro-specific biomarker elevations in neonatal brain injury, aiding in the development of biomarker-based screening tools for early diagnosis and intervention.