The introduction of fluorine atoms into organic molecules has received considerable attention as these organofluorines have often found widespread applications in bioorganic chemistry , medicinal chemistry and biomaterial science. Despite innovation of synthetic C–F forming methodologies, selective fluorination is still extremely challenging. Therefore, a biotransformation approach using fluorine biocatalysts is needed to selectively introduce fluorine into structurally diverse molecules. Yet, there are few ways that enable incorporation of fluorine into structurally complex bioactive molecules. One is to extend the substrate scope of the existing enzyme inventory. Another is to expand the biosynthetic pathways to accept fluorinated precursors for producing fluorinated bioactive molecules. Finally, an understanding of the physiological roles of fluorometabolites in the producing microorganisms will advance our ability to engineer a microorganism to produce novel fluorinated commodities. Here, we review the fluorinase biotechnology and fluorine biocatalysts that incorporate fluorine motifs to generate fluorinated molecules, and highlight areas for future developments.