Neurodegenerative diseases are characterized by premature neuronal loss in specific brain regions. During the past decades our knowledge on molecular mechanisms underlying neurodegeneration has increased immensely and resulted in promising drug candidates that might slow down or even stop the neuronal loss. These advances have put a strong focus on the development of diagnostic tools for early or pre-clinical detection of the disorders. In this review we discuss our experience in the field of neuroproteomics/peptidomics, with special focus on biomarker discovery studies that have been performed on CSF samples from well-defined patient and control populations.