The review focuses on recent advances in the methodologies for the formation or introduction of the CHF moiety in -heterocyclic substrates over the past 5 years. The monofluoromethyl group is one of the most versatile fluorinated groups used to modify the properties of molecules in synthetic medical chemistry. The review summarizes two strategies for the monofluoromethylation of -containing heterocycles: direct monofluoromethylation with simple XCHF sources (for example, ICHF) and the assembly of -heterocyclic structures from CHF-containing substrates. The review describes the monofluoromethylation of pharmaceutically important three-, five- and six-membered -heterocycles: pyrrolidines, pyrroles, indoles, imidazoles, triazoles, benzothiazoles, carbazoles, indazoles, pyrazoles, oxazoles, piperidines, morpholines, pyridines, quinolines and pyridazines. Assembling of 6-fluoromethylphenanthridine, 5-fluoromethyl-2-oxazolines, C5-monofluorinated isoxazoline -oxides, and α-fluoromethyl-α-trifluoromethylaziridines is also shown. Fluoriodo-, fluorchloro- and fluorbromomethane, FCHSOCl, monofluoromethyl(aryl)sulfoniummethylides, monofluoromethyl sulfides, (fluoromethyl)triphenylphosphonium iodide and 2-fluoroacetic acid are the main fluoromethylating reagents in recent works. The replacement of atoms and entire functional groups with a fluorine atom(s) leads to a change and often improvement in activity, chemical or biostability, and pharmacokinetic properties. The monofluoromethyl group is a bioisoster of -CH, -CHOH, -CHNH, -CHCH, -CHNO and -CHSH moieties. Bioisosteric replacement with the CHF group is both an interesting task for organic synthesis and a pathway to modify drugs, agrochemicals and useful intermediates.