Plant microbe interactions encompass the diverse relationships between plants and the microorganisms that inhabit their rhizosphere, phyllosphere, and internal tissues. These interactions can be beneficial, neutral, or pathogenic, shaping plant health, productivity, and resilience. Symbiotic associations, such as those with mycorrhizal fungi and nitrogen-fixing bacteria, enhance nutrient acquisition, promote growth, and improve stress tolerance. Endophytic microbes also play key roles in producing bioactive compounds and stimulating plant defense responses. On the other hand, pathogenic fungi, bacteria, and viruses challenge plant survival by causing diseases that significantly reduce crop yield and quality. Understanding the molecular dialogue between plants and microbes through signaling pathways, recognition receptors, and defense gene activation offers opportunities to develop innovative strategies for crop protection. Advances in genomics, transcriptomics, and metabolomics have greatly expanded our knowledge of these complex interactions. Harnessing beneficial microbes as biofertilizers, biocontrol agents, and growth promoters has emerged as a sustainable alternative to chemical inputs in agriculture. By unraveling the dynamics of plant–microbe interactions, researchers can design resilient cropping systems that support global food security while minimizing environmental impact.