Fluorine-containing organic molecules play a major role in medicinal chemistry, asymmetric synthesis, crop sciences and material sciences. The selective removal of one fluorine atom from a polyfluorinated functional group by C–F activation is a powerful tool for the synthesis of new fluorinated molecules. This proposal is based on the recent discovery of two unprecedented C–F activation processes involving lanthanide metals: (i) the transformation of trifluoromethylated benzofulvenes into difluorovinylindenes and (ii) the selective formation of 1,2,4,5-tetrafluorobenzene from the reaction of ytterbium with pentafluorobenzene. The aim is the understanding of the aforementioned reactions and the screening of their potential for future applications in organic and organometallic chemistry, with a special interest in the synthesis of biologically active compounds. The outcomes should have an important impact on the understanding and use of lanthanide metals in C–F activation processes.