Fluorine-18 (18F, β+; 96.7%, T1/2=109.8 min) is of considerable importance for developing positron emission tomography (PET) ligands for imaging receptor, enzyme, gene expression etc. in brain, tumor, myocardium and other regions or organs due to its optimal decay characteristics. To synthesize 18F-labeled PET ligands, reliable labeling techniques inserting 18F into a target molecule are necessary. [18F]Fluoroalkylation is a useful way of introducing 18F into target molecules containing amino, phenol, thiophenol, and amide functional groups. Here, we review the preparation, reactivity and application of [18F]fluoroalkyl agents for the development of 18Flabeled PET ligands in molecular imaging. [18F]Fluoroalkyl agents have been synthesized by reacting [18F]F- with the corresponding alkyl derivatives containing halogen and sulfonate as leaving groups. After the fluorination reaction, the radiolabeled products with relatively low boiling points were distilled from the reaction mixtures, sometimes added by Sep-Pak or gas chromatography separation. The [18F]fluoromethyl agents have high reactivity with nucleophilic substrates, but many [18F]fluoromethylated compounds are in vitro unstable. To increase the efficiency of [18F]fluoroethylation, [18F]FCH2CH2Br, the most frequently used [18F]fluoroethyl agent, was converted into [18F]FCH2CH2I or [18F]FCH2CH2OTf in situ. Most [18F]fluoromethylated ligands were found to be in vivo unstable due to defluorination. Deuterium substitution for the fluoromethyl group reduced defluorination to an extent. A number of [18F]fluoroethylated PET ligands have been developed for animal evaluation and clinical investigation.