The molecular biology era has allowed the exact definition of the disease-associated-proteins (DAPs). The computational era has analyzed full-length DAPs by antigenicity prediction algorythms based on physico-chemical parameters. Today, proteomics is providing a global comprehensive analysis of defined peptide portions of DAPs. The fine profiling of the disease-associated peptide repertoire is of particular importance in the definition of qualities as antigenicity and immunogenicity, and is a concrete promise of a bench-to-bedside translational research. Identifying the peptide sequences within the DAPs, which may potentially provoke (auto)immune responses, more than ever emerges as the key strategy for effective immunotherapeutical treatments in cancer diseases as well as infectious or autoimmune pathologies. Here I draw a schematic picture of the experimental attempts to define immunogenic peptide portions, describe the principle of sequence uniqueness as a rationale for the subproteomic analysis of DAPs and delineate the possible advantages of a peptide-vaccine approach to the treatment of degenerative, infectious and autoimmune diseases that might be effective and devoid of collateral harmful effects.