Plant-microbe interactions are both symbiotic and antagonistic, and the knowledge of both these interactions is equally important for the progress of agricultural practice and produce. This review gives an insight into the recent advances that have been made in the plant-microbe interaction study in the post-genomic era and the application of those for enhancing agricultural production. Adoption of next-generation sequencing (NGS) and marker assisted selection of resistant genes in plants, equipped with cloning and recombination techniques, has progressed the techniques for the development of resistant plant varieties by leaps and bounds. Genome-wide association studies (GWAS) of both plants and microbes have made the selection of desirable traits in plants and manipulation of the genomes of both plants and microbes effortless and less time-consuming. Stress tolerance in plants has been shown to be accentuated by association of certain microorganisms with the plant, the study and application of the same have helped develop stress-resistant varieties of crops. Beneficial microbes associated with plants are being extensively used for the development of microbial consortia that can be applied directly to the plants or the soil. Next-generation sequencing approaches have made it possible to identify the function of microbes associated in the plant microbiome that are both culturable and non-culturable, thus opening up new doors and possibilities for the use of these huge resources of microbes that can have a potential impact on agriculture.