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Nucleic acid-based fluorinated derivatives, e.g., nucleosides or oligonucleotides connected to highly fluorinated chains or labeled with one or more fluorine atoms, have been investigated recently due to their high potential for biomedical applications. This review deals with recent works on nucleoside and oligonucleotide fluorocarbon amphiphiles as well as with properties and applications of fluorine-labeled oligonucleotide analogues.