Interfacial electrostatic charges are a universal phenomenon in nature. In recent years, interest in the chemical reactivity of electrostatic charges has grown. Interfacial electrostatic charge-driven chemical synthesis reduces the reliance on redox reagents, catalysts, and hazardous solvents, which promotes environmental sustainability and cost-effectiveness in the chemical industry. Electrostatic charges can be generated at the interfaces between solids, liquids, and gases. The chemical properties of electrostatic charges have been observed at interfaces between solids and liquids, and between liquids and gases. This review summarized the chemical reactivity of interfacial electrostatic charges and its mechanisms. Electrostatic charges play a fundamental role in providing electrons and creating electric fields, which in turn induce charge transfer, radical formation, and molecular orientation. We classified the role of interfacial charges in chemical reactions and provided new perspectives. Interfacial electrostatic charges can be generated with mechanical energy input, a power supply and interface transition from solid-liquid to liquid-gas. Redox and catalytic reactions involving inorganic, organic compounds and biomolecules are driven by interfacial electrostatic charges. Electrostatic chemistry mechanisms are currently a subject of debate because there is insufficient experimental evidence. Challenges and opportunities associated with interfacial electrostatic chemistry are discussed. Knowledge of the reactivity of interfacial electrostatic charges could be used to understand electrostatic phenomena in nature, advance green chemistry, and even study the origins of life. We expect this emerging topic will appeal to scientists in disciplines including interfacial chemistry and electrostatics.