For many years now, fluoride contamination in drinking water has been a great global concern. Regular taking of water with high concentrations of fluoride and fluorocarbons induces numerous abnormal conditions in humans including fluorosis. Some effects of fluoride in drinking water may cause social constraints. For instance, severe fluorosis may cause aesthetic concern in humans inducing high browning and disfiguring of human teeth. Thus, the removal of excess fluoride from drinking water (defluorination) is an inevitable procedure. However, defluorination has been majorly achieved using conventional techniques such as the Nalgonda technique among others. These techniques are associated with high running costs, production of secondary pollutants and usage of amounts of chemicals. The use of microbes capable of fluoride removal (microbial remediation) has also been considered a viable alternative to conventional methods. Additionally, the genetically modified strains of microbes have greater potential for the removal of fluoride when compared to the wild strains. Therefore, this chapter aims to provide insights into the biotechnological approaches to fluoride remediation. The introduction part highlights the meaning of fluoride remediation, sources of fluoride in drinking water and the negative health effects associated with drinking water with high concentrations of fluoride. The chapter further explains the advancement in microbial bioremediation, the chapter explains the role of CRISPR-Cas, and TALEN transcriptional activators in engineering microbes to mitigate environmental pollutants The chapter also discusses the role of genetic and metabolic engineering in bioremediation. Finally, the chapter provides a critical discussion of biotechnological techniques that can be employed to produce the genetic microbes for the bioremediation of fluoride from drinking g water. These approaches include mutation, site-induced mutagenesis, protoplast fusion and metagenomics.