The time is ripe for staging the Human Immunopeptidome Project, whose goal is to analyze the full repertoires of peptides bound to the HLA molecules, in both health and disease. Mass spectrometry technologies have matured to enable comprehensive analyses of both the membrane-bound and the plasma soluble immunopeptidomes associated with each of the HLA allomorphs and the different diseases. The expected outcomes of such project will include basic understanding of the molecular mechanisms involved with formation of immunopeptidomes, correlating them with their source cellular proteomes, definition of both the consensus motifs and the scope of each allomorphs-specific immunopeptidomes, and most importantly, identification of disease-related HLA peptides, which may eventually serve as biomarkers or immunotherapeutics. Ideally, the Human Immunopeptidome Project will become public and the gathered data will be shared, as soon as possible. Other immunopeptidome projects, of other animals, will follow suit.