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Resistant pollutants like oil, grease, pharmaceuticals, pesticides, and plastics in wastewater are difficult to be degraded by traditional activated sludge methods. These pollutants are prevalent, posing a great threat to aquatic environments and organisms since they are toxic, resistant to natural biodegradation, and create other serious problems. As a high-efficiency biocatalyst, enzymes are proposed for the treatment of these resistant pollutants. This review focused on the roles and applications of enzymes in wastewater treatment.