The Human Proteome Organisation was launched in February 2001 as a result of the need of an international proteomic forum to improve the understanding of human diseases. The initiative dealing with the brain is the Human Proteome Organisation Brain Proteome Project chaired in Germany and Korea. In order to estimate the existing approaches in brain proteomics, as well as to establish a standardized data reprocessing pipeline, pilot studies were initiated including both mouse and human samples. Data had to be submitted to a Data Collection Center for central re-processing and are now publicly accessible at the PRIDE database serving as reference data for future analysis. It became clear that heterogeneity, for example, different analysis strategies and data formats, are a real challenge when comparing results and when working in a consortium. Therefore, standardization, the organisation of data management and the synergistic effects of a consortium of collaborators are of outstanding importance to any big proteome analysis. The following manuscript will highlight these activities and aims of the Human Proteome Organisation Brain Proteome Project, summarizing its historical timeline and its two pilot studies.