Not much more than 15 years ago a handful of visionary scientists around the world suggested to sequence and analyze not only the human genome but also as many genomes as possible in order to compare DNA as well as to deduce protein sequences. By that means they expected to get an idea about the organization of life. However, after now having now sequenced the human genome and at least identified around 40,000 genes as coding regions, we are still left with the fundamental questions of how genes are regulated, and what is the rationale of genetic regulatory networks. The basic knowledge and methodologies to elucidate functional regulatory networks of cells and organisms on the protein level had been around for much longer than DNA-based discovery tools. This was mainly due to the fact that proteins have to fulfill universal functions in nature and, unlike DNA polynucleotides, proteins differ not only in their amino acid sequences; they come in nearly all shapes and sizes and have all kinds of physical as well as chemical properties. They can be highly water soluble, e.g., serum and milk proteins, or nearly insoluble in any solvent, e.g., keratin and some other structural proteins. In addition, structure, function, as well as the respective stability of proteins inside and outside of a biological system, are individual features of any given polypeptide. On one hand, the individuality of proteins allows adaptation of any life form to the environment, and on the other it is still a real challenge for biotech R&D and production. The present review is actually the first approach to evaluate and judge the achievements made by Applied Proteome Analysis and Proteomics over the last 27 years.