It is possible to summarized that Organofluorine compounds are organic compounds that contain carbon and fluorine bonded in the polarized and remarkably strong carbon–fluorine bond. Naturally occurring organofluorine compounds are less abundant in the atmosphere, and there are only about thirty natural organofluorine compounds that have been identified from both biogenic and abiogenic sources. Different sample preparation techniques exist for the determination of organofluorine compounds in a wide range of matrices; the types of matrix, the extraction/derivatization procedures, the analytical methods, and the analyte concentrations. However, there are unsolved issues concerning organofluorine compounds like the sources of some natural organofluorine compounds; the analytical techniques for quantification; ways of extracting them without altering their chemical composition and preventing contamination of samples. Moreover, there is no literature review that shows the quantification and characterization of naturally occurring organofluorine compounds in the environmental and biological samples in Ethiopia. Therefore, research is needed to assess their environmental impact.