The saga of the search for the ultimate constituents of matter has long been one of finding a seemingly fundamental structure that, in turn, was found to be made of even smaller building blocks. Matter is made of molecules. Molecules are in turn made of atoms, which are themselves made of electrons and atomic nuclei. The nucleus consists of protons and neutrons, and these nucleons are composed of quarks. The author discusses this search and concludes with a reflection that the mystery of quark and lepton generations and the question of substructure is a real one and one without any known answer. Unlike the Higgs mechanism or supersymmetry, this conundrum does not have an established and popular prospective solution.