Plant-associated microorganisms are involved in important functions related to growth, performance and health of their hosts. Understanding their modes of action is important for the development and application of microbial bioprotectants and biostimulants. Recent studies have revealed manifold plant-microbe as well as pathogen-microbe interactions, which form the basis of understanding beneficial effects of plant-associated microorganisms. Microbiome research has contributed to our understanding of the modes of action of various plant-associated microorganisms. This chapter summarizes current knowledge about beneficial plant-microbe interactions, discusses recent insights into the functioning of the plant microbiome and beneficial plant-microbe networks. It shows that the use of microorganisms and the exploitation of beneficial plant–microbe interactions offer promising and environmentally-friendly strategies to achieve sustainable agriculture on a global scale.