The introduction of new-generation immunoassay methods has enabled the reliable quantification of neurofilament light chain (NFL) levels in peripheral matrices, making it a promising blood marker for active brain pathology. NFL, a neuron-specific cytoskeletal component, is released into extracellular matrices after neuroaxonal impairment and has been suggested as a highly sensitive but unspecific tool for quantifying brain pathology. While NFL has been extensively studied in neurological conditions, its role as a biomarker in major psychiatric disorders is less explored. This review aims to introduce NFL as a marker of neuroaxonal injury and systematically review recent findings on NFL levels in primary psychiatric conditions. Current evidence suggests elevated blood NFL levels in patients with major depression, bipolar disorder, psychotic disorders, anorexia nervosa, and substance use disorders compared to physiological states. However, NFL levels vary significantly across diagnostic entities, clinical stages, and patient subgroups, influenced by demographic, clinical, and analytical factors. Potential clinical applications of NFL in psychiatry include diagnostic algorithms, excluding neurodegenerative diseases, assessing brain toxicity for pharmacological compounds, and monitoring treatment response. The high inter-individual variability and the lack of understanding of the neurobiological significance of NFL release are major limitations. Overall, this primer aims to guide researchers and clinicians in the use of NFL measure in psychiatric research and provide a conceptual framework for future studies.The introduction of new-generation immunoassay methods has enabled the reliable quantification of neurofilament light chain (NFL) levels in peripheral matrices, making it a promising blood marker for active brain pathology. NFL, a neuron-specific cytoskeletal component, is released into extracellular matrices after neuroaxonal impairment and has been suggested as a highly sensitive but unspecific tool for quantifying brain pathology. While NFL has been extensively studied in neurological conditions, its role as a biomarker in major psychiatric disorders is less explored. This review aims to introduce NFL as a marker of neuroaxonal injury and systematically review recent findings on NFL levels in primary psychiatric conditions. Current evidence suggests elevated blood NFL levels in patients with major depression, bipolar disorder, psychotic disorders, anorexia nervosa, and substance use disorders compared to physiological states. However, NFL levels vary significantly across diagnostic entities, clinical stages, and patient subgroups, influenced by demographic, clinical, and analytical factors. Potential clinical applications of NFL in psychiatry include diagnostic algorithms, excluding neurodegenerative diseases, assessing brain toxicity for pharmacological compounds, and monitoring treatment response. The high inter-individual variability and the lack of understanding of the neurobiological significance of NFL release are major limitations. Overall, this primer aims to guide researchers and clinicians in the use of NFL measure in psychiatric research and provide a conceptual framework for future studies.