Sulfolane is widely used around the world as an industrial solvent for purifying sour natural gas. However, because of accidental spillage and improper on-site storage/disposal procedures, reports of groundwater, aquifer, and soil contaminations have raised concerns about its potential impacts on humans and the ecosystem. As a contaminant of emerging concern, there is a lack of information on the human toxicity of sulfolane. Several bioremediation technologies have been conducted to assess the biodegradation potential of sulfolane in contaminated groundwater and soils. This review presents and discusses the available literature on the toxicity of sulfolane, which could be useful for developing proper sulfolane guidelines in different media. The oral LD50 of sulfolane varies from 0.6 to 3.5 g·(kg body mass)–1 for different mammalian species, including guinea pig, mouse, rabbit, and rat. In addition, we also review the various sulfolane bioremediation studies to date, highlighting the efficacy of aerobic versus anaerobic bioremediation of sulfolane at contaminated sites. The zero-order biodegradation rate of sulfolane varies from 0.033 to 190 mg·L–1·day–1 depending on the initial concentration of sulfolane, nutrients, oxygen levels, temperature, and other parameters. Effective aerobic treatment technologies can lead to the complete mineralization of sulfolane with sulfuric acid as its major end by-product. Furthermore, the application of aerobic granulation as a promising biotechnology for sulfolane biodegradation is also discussed. This review further discusses the significance of utilizing sulfolane-degrading bacteria to reduce treatment times and presents information for future researchers and scientists on the specific isolates recorded.