The past decade has seen tremendous efforts in biomarker discovery and validation for neurodegenerative diseases. The source and type of biomarkers has continued to grow for central nervous system diseases, from biofluid-based biomarkers (blood or cerebrospinal fluid (CSF)), to nucleic acids, tissue, and imaging. While DNA remains a predominant biomarker used to identify familial forms of neurodegenerative diseases, various types of RNA have more recently been linked to familial and sporadic forms of neurodegenerative diseases during the past few years. Imaging approaches continue to evolve and are making major contributions to target engagement and early diagnostic biomarkers. Incorporation of biomarkers into drug development and clinical trials for neurodegenerative diseases promises to aid in the development and demonstration of target engagement and drug efficacy for neurologic disorders. This review will focus on recent advancements in developing biomarkers for clinical utility in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).