It seems that many enzymes have broader specificity than what was originally thought. This very broad specificity exhibited in different contexts has great significance for their biological functions. A practical application of this is that robust affinity ligands, with no biological relationship, are used in industrial enzymology. Moonlighting protein and biological promiscuity are the in vivo phenomena exploiting this broad specificity. Similarly, both order and disorder in protein structure are biologically relevant. Intrinsically disordered proteins (IDPs) seem to indicate the same. Enzyme catalysis in nearly anhydrous organic solvents is an example of condition promiscuity. Some IDPs show moonlighting property and promiscuity in molecular recognition. It is time to revisit concepts of native structure, biological specificity and even binding site.