Plant disease resistance genes play a pivotal role in defending crops against pathogens, and safeguarding global food security.  Plant disease resistance genes are crucial components of plant immunity, playing a pivotal role in protecting crops against many pathogens. This review delves into recent advancements in understanding the mechanisms, evolutionary dynamics, and applications of plant disease-resistance genes in agriculture. It explores the intricate molecular pathways involved in plant-pathogen interactions, highlighting recent discoveries in plant immune system components and their regulation. The review also examines the evolutionary dynamics of resistance genes, including gene duplication, diversification, and co-evolution with pathogens, shedding light on adaptive strategies employed by plants. Furthermore, it discusses emerging gene discovery and characterization technologies, such as genomic, transcriptomic, and proteomic approaches, and their implications for accelerating crop breeding efforts. The review emphasizes the practical applications of disease-resistance genes in crop improvement, including strategies for incorporating resistance genes into breeding programs and deploying resistant cultivars. Additionally, it discusses the broader implications of harnessing resistance genes for sustainable agriculture, biodiversity conservation, and global food security. By synthesizing interdisciplinary research findings, this review provides valuable insights into the future directions of utilizing plant disease-resistance genes for crop protection and productivity in a changing agricultural landscape.