This review article discusses the potential of neurofilament light chain (NfL) as a blood biomarker for neuroaxonal injury in psychiatric conditions. NfL, a neuron-specific cytoskeletal protein, is released into extracellular matrices after neuroaxonal damage and has been suggested as a sensitive marker of active brain pathology. Recent studies have shown elevated blood NfL levels in patients with major depression, bipolar disorder, psychotic disorders, anorexia nervosa, and substance use disorders compared to healthy individuals. However, NfL levels vary significantly across diagnostic entities, clinical stages, and patient subgroups, and are influenced by demographic, clinical, and analytical factors. Potential clinical applications of NfL in psychiatry include diagnostic and prognostic algorithms, exclusion of neurodegenerative disease, assessment of brain toxicity for pharmacological compounds, and longitudinal monitoring of treatment response. Despite its promise, NfL levels show high inter-individual variability and the neurobiological mechanisms of its release are not fully understood. The review highlights the opportunities and pitfalls of using NfL in psychiatric conditions, emphasizing the need for standardized study settings, high-sensitive assays, and correction for demographic and clinical factors. The article also discusses the current evidence on NfL levels in various psychiatric disorders, including major depressive disorder, bipolar disorder, psychotic disorders, and substance use disorders, and highlights the potential of NfL as a tool for longitudinal monitoring and treatment response assessment. The review concludes that while NfL has the potential to be a valuable biomarker in psychiatry, further research is needed to fully understand its role and applications.This review article discusses the potential of neurofilament light chain (NfL) as a blood biomarker for neuroaxonal injury in psychiatric conditions. NfL, a neuron-specific cytoskeletal protein, is released into extracellular matrices after neuroaxonal damage and has been suggested as a sensitive marker of active brain pathology. Recent studies have shown elevated blood NfL levels in patients with major depression, bipolar disorder, psychotic disorders, anorexia nervosa, and substance use disorders compared to healthy individuals. However, NfL levels vary significantly across diagnostic entities, clinical stages, and patient subgroups, and are influenced by demographic, clinical, and analytical factors. Potential clinical applications of NfL in psychiatry include diagnostic and prognostic algorithms, exclusion of neurodegenerative disease, assessment of brain toxicity for pharmacological compounds, and longitudinal monitoring of treatment response. Despite its promise, NfL levels show high inter-individual variability and the neurobiological mechanisms of its release are not fully understood. The review highlights the opportunities and pitfalls of using NfL in psychiatric conditions, emphasizing the need for standardized study settings, high-sensitive assays, and correction for demographic and clinical factors. The article also discusses the current evidence on NfL levels in various psychiatric disorders, including major depressive disorder, bipolar disorder, psychotic disorders, and substance use disorders, and highlights the potential of NfL as a tool for longitudinal monitoring and treatment response assessment. The review concludes that while NfL has the potential to be a valuable biomarker in psychiatry, further research is needed to fully understand its role and applications.