Exploring the proteome on a system-wide level is essential for obtaining information on the molecular mechanisms of diseases and fundamental biological processes. Proteomics has made tremendous advances to study the cellular repertoire of proteins in its entirety, but capturing representative proteomes in fundamental biology is still an elaborate process. To replace an outdated instrument, the Proteomics Core Facility of the Biozentrum of the University of Basel applies for a new, state-of-the-art Orbitrap Fusion mass spectrometer. The instrument will be made available to all interested groups of the Biozentrum. We envisage to devote the instrument to a number of key projects that range from cancer biology to basic research of cellular trafficking and pathophysiology. The data generated with this state-of-the-art instrument will expand our knowledge in many areas of biology, disease, and diagnostics.