AbstractPoly(ethylene terephthalate) (PET) is one of the most widely used synthetic polyesters, but also a major cause of plastic pollution. Because the chemical degradation of PET would be uneconomical and rather burdensome, considerable efforts have been devoted to exploring enzymatic processes for the disposal of PET waste. Many PET‐hydrolyzing enzymes have been reported in recent decades, some of which demonstrate excellent potential for industrial applications. This review sets out to summarize the state of investigation into IsPETase, a cutinase‐like enzyme from Ideonella sakaiensis possessing ability to degrade crystalline PET, and to gain further insight into the structure–function relationship of IsPETase. Benefiting from the continuing identification of novel cutinase‐like proteins and growing availability of the engineered IsPETase, we may anticipate future developments in this type of enzyme would generate suitable biocatalyst for industrial use.