Chelating agents show very effective performance in different applications in the upstream oil and gas industry. This study presents a critical review of the application of chelating agents in acidizing, scale removal, filter cake removal, wettability alteration, enhanced oil recovery (EOR), and hydraulic fracturing treatments. The advantages and disadvantages of using several types of chelating agents for improving the well/reservoir productivity and enhancing the oil recovery from sandstone and carbonate reservoirs are discussed. Also, detailed comparisons between different chelating agents and their applications in many oil and gas areas are presented. Moreover, the combination of chelating agents with different chemicals to achieve better performance is addressed. Hydroxy amino carboxylic acids [such as ethylenediaminetetraacetic acid (EDTA) and glutamic acid diacetic acid (GLDA)] have replaced conventional acids, such as hydrochloric acid (HCI), hydrofluoric acid (HF), and organic acids, at high temperature and salinity conditions to stimulate carbonate and sandstone reservoirs without any side effects on the formation integrity. Furthermore, diethylenetriaminepentaacetic acid (DTPA) and GLDA are effective in removing different types of scales, such as carbonate, sulfate, and sulfides, without releasing hydrogen sulfide (H2S) and using corrosion inhibitors. Also, DTPA, EDTA, and GLDA are very active in dissolving filter cake layers formed by different drilling fluids. Aminopolycarboxylic groups can be injected into sandstone and carbonate reservoirs to adjust the wettability conditions and enhance oil recovery. Chelating agents, such as GLDA, EDTA, and DTPA, optimize the fracture conductivity and, meanwhile, minimize the number of additives in hydraulic fracturing, which significantly cut the cost of the operation. Overall, chelating agents are economically attractive chemicals for various upstream operations since produced, and seawater can be used without further treatment.