The interaction between plants and microbes is pivotal to sustainable agriculture, encompassing mutualistic, pathogenic, and commensurate interactions. Plants and microbes communicate chemically through various molecules, including phytohormones, secondary metabolites, and quorum-sensing molecules. These molecules play a significant role in plant defence, growth, and microbial communication. A plant's defence mechanisms against pathogens involve identifying pathogen-associated molecular patterns (PAMPs) and triggering effector-triggered immunity (ETI), as well as activating hypersensitive reactions and systemic acquired resistance through resistance (R) proteins. In addition to contributing to the antimicrobial activity of plants, phytoalexins induce systemic resistance as well. Beneficial plant-microbe interactions, including those with plant growth-promoting rhizobacteria, mycorrhizal associations, and endophytic microbes, offer potential for sustainable agriculture by enhancing nutrient uptake, stress tolerance, and crop productivity. These interactions reduce reliance on chemical fertilizers and pesticides, enhance crop resilience, and offer bioremediation potential. However, understanding the complexity of plant-microbe interactions and developing targeted strategies for manipulating these interactions present challenges. Future research directions include exploring the potential of synthetic biology, addressing ethical and regulatory considerations, and leveraging the benefits of plant-microbe interactions for sustainable agriculture. The review provides a comprehensive overview of the current understanding of plant-microbe interactions and highlights the importance of further research in harnessing these interactions for sustainable agriculture.