Recent successes in the identification of biomarkers and therapeutic targets for diagnosing and managing neurological diseases underscore the critical need for cutting-edge biobanks in the conduct of high-caliber translational neuroscience research. Biobanks dedicated to neurological disorders are particularly timely, given the increasing prevalence of neurological disability among the rising aging population. Translational research focusing on disorders of the central nervous system (CNS) poses distinct challenges due to the limited accessibility of CNS tissue pre-mortem. Nevertheless, technological breakthroughs, including single-cell and single-nucleus methodologies, offer unprecedented insights into CNS pathophysiology using minimal input such as cerebrospinal fluid (CSF) cells and brain biopsies. Moreover, assays designed to detect factors that are released by CNS resident cells and diffuse into the CSF and/or bloodstream (such as neurofilament light chain [NfL], glial fibrillar acidic protein [GFAP] and amyloid beta peptides), and systemic factors that cross the blood–brain barrier to target CNS-specific molecules (e.g., autoantibodies that bind either the NMDA receptor [NMDAR] or myelin oligodendrocyte glycoprotein [MOG]), are increasingly deployed in clinical research and practice. This review provides an overview of current biobanking practices in neurological disorders and discusses ongoing challenges to biomarker discovery. Additionally, it outlines a rapid consenting and processing pipeline ensuring fresh paired blood and CSF specimens for single-cell sequencing that might more accurately reflect in vivo pathways. In summary, augmenting biobank rigor and establishing innovative research pipelines using patient samples will undoubtedly accelerate biomarker discovery in neurological disorders.