Chlorine dioxide (ClO2) has emerged as a broad-spectrum, safe, and effective disinfectant due to its high oxidation efficiency and reduced formation of organochlorinated by-products during application. This article provides an updated overview of ClO2-based oxidation processes used in water treatment. A systematic review of scientific information and experimental data on ClO2-based water purification procedures is presented. Concerning ClO2-based oxidation derivative problems, the pros and cons of ClO2-based combined processes are assessed and disinfection by-product (DBP) control approaches are proposed. The kinetic and mechanistic data on ClO2 reactivity towards micropollutants are discussed. ClO2 selectively reacts with electron-rich moieties (anilines, phenols, olefins, and amines) and eliminates certain inorganic ions and microorganisms with high efficiency. The formation of chlorite and chlorate during the oxidation process is a crucial concern when utilizing ClO2. Future applications include the combination of ClO2 with ferrous ions, activated carbon, ozone, UV, visible light, or persulfate processes. The combined process can reduce by-product generation while still ensuring ClO2 sterilization and disinfection. Overall, this research could provide useful information and new insights into the application of ClO2-based technologies.