AbstractThe commercialization of fuel cells, such as proton exchange membrane fuel cells and direct methanol/formic acid fuel cells, is hampered by their poor stability, high cost, fuel crossover, and the sluggish kinetics of platinum (Pt) and Pt‐based electrocatalysts for both the cathodic oxygen reduction reaction (ORR) and the anodic hydrogen oxidation reaction (HOR) or small molecule oxidation reaction (SMOR). Thus far, the exploitation of active and stable electrocatalysts has been the most promising strategy to improve the performance of fuel cells. Accordingly, increasing attention is being devoted to modulating the surface/interface electronic structure of electrocatalysts and optimizing the adsorption energy of intermediate species by defect engineering to enhance their catalytic performance. Defect engineering is introduced in terms of defect definition, classification, characterization, construction, and understanding. Subsequently, the latest advances in defective electrocatalysts for ORR and HOR/SMOR in fuel cells are scientifically and systematically summarized. Furthermore, the structure–activity relationships between defect engineering and electrocatalytic ability are further illustrated by coupling experimental results and theoretical calculations. With a deeper understanding of these complex relationships, the integration of defective electrocatalysts into single fuel‐cell systems is also discussed. Finally, the potential challenges and prospects of defective electrocatalysts are further proposed, covering controllable preparation, in situ characterization, and commercial applications.