Defect engineering have demonstrated promise in heterogeneous persulfate activation for water remediation, yet the underling mechanisms of defects remain ambiguous. This review describes the cutting-edge progress of defects in persulfate activation regimes. The primary emphasis lies in deciphering how defects impact the catalytic kinetics of persulfate by serving as adsorption sites, regulating electronic structure and thus affecting adsorption energies, inducing surface reconstitution, and providing bonding sites for creating new active centers. Moreover, methodologies for identifying defects (e.g., advanced characterization techniques, defect screening, and theoretical calculations) are outlined alongside strategies for manufacturing tailored defects through in-situ synthesis and post-processing methods. Strikingly, the role of defects in switching persulfate activation pathways is highlighted, illuminating the design of tailored defective catalysts for diverse environmental scenarios. Concluding with a forward-looking perspective envisaging critical challenges and insights for defect design, mechanistic exploration, and practical implementation.