Heterogeneous catalysis plays an important role in modern industry. Exploring catalysts with high efficiency, low-cost, and high stability is an important issue for the research of heterogeneous catalysis. In recent years, researchers have prepared a variety of defective catalysts and found that the defects in catalysts have an important effect on their catalytic activity. However, the relationship between defects and catalytic activity remains to be clarified. In this Review, three aspects including recognition, understanding, and utilization for defect chemistry in heterogeneous catalysis have been proposed. Based on recent progress, this work mainly introduces the fundamental concept, types, and characterization of defects in catalysts, significant effects of defects on catalytic properties, and controllable construction methods of defects for efficient catalyst synthesis. Finally, the conclusion and outlook for the research of defect chemistry in heterogeneous catalysis are presented. It is hoped that this work can provide guidance for the controllable synthesis and mechanism research of defective heterogeneous catalysts.