For QSAR/QSPR studies, topological indices have proved to be among the most useful molecular descriptors. They are based on local vertex invariants (LOVIs). A review of last-generation real-number Tls based on new real-number LOVIs is presented. It is possible to reduce thus the intramolecular degeneracy of LOVIs for nonequivalent vertices, and the intermolecular degeneracy of TIs for nonisomorphic molecular graphs. The correlation ability of TIs was tested by modeling physico-chemical properties of large classes of compounds (alkanes, haloalkanes, compounds with oxygen or sulfur heteroatoms), or smaller sets of biologically active compounds. Prospects for modeling thermodynamic properties of chlorofluorocarbons and congeners are discussed.