Biomarkers are needed to overcome critical roadblocks in the development of disease-modifying therapeutics for neurodegenerative diseases. Evolving genome-wide expression technologies can comprehensively search for molecular biomarkers and allow fascinating insights into the expanding complexity of the human transcriptome. The technology has matured to the point where some applications are deemed reliable enough for use in patient care. In the neurosciences, it has led to the discoveries of osteopontin in multiple sclerosis and SORL1/LR11 in Alzheimer's, and recent studies indicate its potential for identifying neurogenomic biomarkers. Advances in pre-analytical and analytical methods are improving search efficiency and reproducibility and may lead to a pipeline of biomarker candidates suitable for development into future neurologic diagnostics.