Defense heterosis as a novel plant protection strategy: From theory to breeding practice

Abstract Plant diseases cause severe yield losses annually, threatening global food security. Traditional resistance breeding faces challenges such as rapid pathogen evolution and yield‐defense trade‐offs. Defense heterosis—the phenomenon where F 1 hybrids derived from crosses between genetically distinct parental lines exhibit superior disease resistance compared to parents—provides a promising solution. This review summarizes recent advances in understanding defense heterosis, from its conceptual evolution to modern genomic insights. Here, we outline three classical genetic hypotheses (dominance, overdominance, and epistasis) and introduce molecular mechanisms, including differentially expressed genes, epigenetic regulation (DNA methylation, histone modifications), and salicylic acid‐mediated coordination of immunity. Case studies across rice, maize, wheat, and potato demonstrate the prevalence and variability of defense heterosis. We highlight that future efforts should utilize multiomics data, genome editing, and microbiome manipulation to predict and deploy defense heterosis. This integrated perspective bridges fundamental research and agricultural applications, offering a roadmap to enhance crop resilience and food security.