Biomarkers of brain disorders are urgently needed to aid diagnosis, monitor disease progression, and, as new medicines are introduced, detect the patient's response to treatment. Proteomics provides the opportunity to discover novel biochemical markers based on protein or peptide changes, either in concentration levels or post-translational modification status. There are many challenges associated with proteomics studies, and this article represents a review of the issues discussed during the proteomics breakout sessions held at the Biomarkers for Brain Disorders conference in Oxford in January 2009. Although to date, there are very few qualified biomarkers that have arisen as a result of proteomics efforts, we remain optimistic that proteomics will deliver biomarkers for brain disorders. To be successful, we need to recognize that such endeavors are likely to require multidisciplinary teams and continued collaboration between academia, the biotechnology industry, and the pharmaceutical sector.