This literature review provides insights into the natural occurrence of fluorinated organic compounds, their chemical properties, their history and applications, associated risks and benefits, and policy approaches for sustainable and safe uses in the future. Owing to their unique chemical properties and widespread uses, organofluorines are indispensible in modern society. However, their environmental persistence, toxicity and bioaccumulation potential also pose considerable risks to the environment and human populations. Less than a dozen organofluorines are known to occur naturally whereas manmade organofluorines figure in the hundreds. This implies that the large-scale environmental release of manmade organofluorines is an ongoing experiment the consequences and implications of which are as of yet poorly understood. However, available data indicate organofluorines to be more persistent and more toxic than their non-fluorinated counterparts. Reviewed in detail are the history of production and regulation of chlorofluorocarbons (CFCs), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA). Unforeseen risks to the environment and human health are discussed and shown, at least for some organofluorines, to outweigh their respective economic benefits. In 1989, the Montreal Protocol on Ozone Depleting Substances banned the use of CFCs by international agreement. In 2006, the 2010/15 PFOA Stewardship Program began, with the intention of reducing PFOA emissions by 95% by 2010 and achieving a complete phase-out of PFOA by 2015. In May of 2009, the Stockholm Convention on persistent organic pollutants (POPs) recognized PFOS as a POP and restricted its use to specific industrial applications. These three compounds represent only a small number of the organofluorines in production, however. Further investigations are warranted into other members of this family of persistent chemicals. The bioaccumulation potential, capacity for long-range transport, toxicity and persistence of organofluorines challenge human society to carefully manage chemical production and releases. To stem the ongoing accumulation of anthropogenic fluorinated compounds in the environment, the chemical industry should be incentivized to develop organofluorine replacements that resemble naturally occurring compounds and for which natural degradation pathways exist. Implementing this and similar more sustainable practices, derived from the precautionary principle, will aid in eliminating or significantly reducing unwanted ecological and human health risks.