About twenty years ago, the cofactor pyrroloquinoline quinone, PQQ, was discovered. Here the author gives his personal view on the reasons why this cofactor was so lately discovered and how the steps in its identification were made. The discovery not only led to subsequent studies on the physiological significance of PQQ but also initiated investigations on other enzymes where the presence of PQQ was expected, resulting in the discovery of three other quinone cofactors, TPQ, TTQ, and LTQ, which differ from PQQ as they are part of the protein chain of the enzyme to which they belong. Enzymes using quinone cofactors, the so-called quinoproteins, copper-quinoproteins, and quinohemoproteins, are mainly involved in the direct oxidation of alcohols, sugars, and amines. Some of the PQQ-containing ones participate in incomplete bacterial oxidation processes like the conversion of ethanol into vinegar and of D-glucose into (5-keto)gluconic acid. Soluble glucose dehydrogenase is the sensor in diagnostic test strips used for glucose determination in blood samples of diabetic patients. Quinohemoprotein alcohol dehydrogenases have an enantiospecificity suited for the kinetic resolution of racemic alcohols to their enantiomerically pure form, certain enantiomers being interesting candidates as building block for synthesis of high-value-added chemicals. Making up for balance after twenty years of quinoprotein research, the following conclusions can be drawn: since quinoproteins do not catalyze unique reactions, we know now that there are more enzymes which catalyze one and the same reaction than we did before, but do not understand the reason for this (compare e.g. NAD/NADP-dependent glucose dehydrogenases, flavoprotein glucose oxidase/dehydrogenase, and soluble/membrane-bound, PQQ-containing glucose dehydrogenases, enzymes all catalyzing the oxidation of beta-D-glucose to delta-gluconolactone but being quite different from each other); however, taking a pragmatic point of view, the foregoing can also be regarded as a positive development since as illustrated by the examples given above, the enlargement of the catalytic arsenal with quinoprotein enzymes provides in more possibilities for enzyme applications; the hopes that PQQ could be a new vitamin have diminished strongly after it has become clear that its occurrence is restricted to bacteria; the impact factor is broader than just the development of the field of quinoproteins, since together with that of enzymes containing a one-electron oxidized amino acid residue as cofactor, it has emphasized that cofactors not only derive from nucleotides (e.g. FAD, NAD) but also from amino acids. Finally, strong indications exist to assume that this is not the end of the story since other quinone cofactors seem awaiting their discovery.