The plant microbiome, which is the diverse community of microorganisms that exists in and around plant tissue, influences the health, productivity, and stress resistance of plants. These microorganisms, especially in the rhizosphere, phyllosphere, and endosphere, contribute to nutrient uptake, hormone regulation, immune function modulation, and resistance against pathogens. The structure, origin, and functional diversity of the microbiota inhabiting plants, and particularly their roles in growth promotion and in the enhancement of plant tolerance to biotic and/or abiotic stresses, will be extensively discussed in this chapter. Special attention is given to the mechanisms by which beneficial microbes suppress plant pathogens, including parasitism, competition, secretion of lytic enzymes and antibiotics, and induction of host defenses. The main challenges surrounding the microbiome-plant host-pathogen interactions linked to abiotic stress are also considered. The chapter finally concludes with the opportunities of using the plant microbiome for sustainable agriculture and focuses on the future perspectives of microbiome engineering and bio-control in the integrated crop management.