Organofluorine　compounds　find　extensive　application　in　the　fields　of　agrochemicals,　pharmaceuticals,　materials　science,　and　molecular　imaging.　Introducing　fluorine　atoms　can　provide　organic　compounds　with　unique　physicochemical　properties　or　improve　their　biological　activity.　Although　significant　progress　has　been　made　in　the　chemical　synthesis　of　fluorine-containing　compounds,　achieving　selective　fluorination　under　mild　conditions　remains　extremely　challenging.　Introducing　biocatalytic　approaches　in　organofluorine　chemistry　is　an　important　strategy　given　their　high　efficiency,　selectivity,　and　environmental　friendliness.　In　this　review,　we　present　the　discovery　of　fluorinated　natural　products　and　fluorinases,　the　crystal　structure　and　the　directed　evolution　of　fluorinases,　with　a　focus　on　recent　advances　in　the　enzymatic　synthesis　of　fluorine-containing　compounds　in　recent　years.　It　is　hoped　that　this　review　will　help　to　promote　the　field　of　biocatalytic　organofluorine　compound　synthesis.　©　2024　Wiley-VCH　GmbH.