(3.2.6) Grimme : Chemically relevant energies span a huge range -from one tenth to hundreds of kcal/mol. The often cited "chemical accuracy" of 1 kcal/mol usually refers to bond or atomization energies, which (for small systems) are on the order of a few hundred kcal/mol. While this definition is appropriate for some thermochemical problems, it is inappropriate for others. For example, the very relevant conformational energies of typical pharmaceutical drug molecules with about 50 atoms are on the order of the thermal energy at room temperature (0.6 kcal/mol). Hence, in practical applications, only errors less than about 0.1-0.2 kcal/mol are acceptable. Another aspect to consider here is that the most important primary application of current Kohn-Sham DFT in chemistry is probably the determination of equilibrium structures (R e ) including those of chemical transition states. Even with rather simple DFAs (e.g., GGAs), basically no severe outliers are obtained, even in electronically difficult cases -a fact that, in retrospect, was extremely important for the development of computational chemistry. As such, newly proposed, empirical DFAs, should be carefully tested not only for energies but additionally for the computation of R e structures. Similar considerations hold for the computation of vibrational frequencies, which are of utmost importance