AbstractPlant pathogens cause plant diseases that significantly decrease crop yields, posing a serious threat to global food security. While plant disease resistance has traditionally been understood as the trait determined by the plant innate immune system and the pathogen virulence system, recent research underscores the pivotal role of the plant microbiome in disease resistance. Plant-associated microbiomes confer protection against pathogens through direct pathogen inhibition, resource competition, and activation of plant immune responses. Agricultural practices such as crop rotation, intercropping, disease-resistant breeding, biocontrol, and organic farming modulate plant microbiomes, thereby influencing disease resistance. This review synthesizes the latest advancements in understanding the intricate interactions among plants, pathogens, and microbiomes. We emphasize the need for in-depth mechanistic studies linking agricultural practices to microbiome dynamics and propose future research directions to leverage microbiomes for sustainable agriculture.