Over the past decade, there has been a surge in the interest in identifying, developing, and implementing biofluid-based biomarkers to enhance the diagnostic process for neurodegenerative diseases. This interest has been partly driven by the advent of highly sensitive detection techniques and disease-modifying therapies, underscoring the necessity for reliable, cost-effective, and easily obtainable biofluid-based biomarkers. These biomarkers would be essential for facilitating the development and monitoring of such therapies and for selecting appropriate participants for clinical trials. In this review, we will discuss the significance of various biofluid-based biomarkers, with the emphasis on neurofilament light, including those indicative of neuronal cell-body damage (neuron-specific enolase and ubiquitin C-terminal hydrolase-L1) and axonal damage (neurofilament proteins and myelin basic protein). Additionally, we will explore the integration of novel biomarkers into clinical practice and trials, highlighting their potential to revolutionize the management of neurodegenerative diseases. This chapter aims to provide a comprehensive overview of the current landscape and future prospects of biofluid biomarkers in neurodegenerative disorders.