Microbial endophytes inhabit the internal tissues of all land plants. These microorganisms tightly interact with their hosts and have a significant impact on their health, development, growth and overall fitness. The deluge of second-generation sequencing data has also provided information of the genomes of endophytes and on the composition of microbial communities in plants. We adopted grapevine as a model plant to study microbial interactions in perennial plants as this is both widely available in the Mediterranean area and in several locations around the world, and because it is an important fruit crop carrying an invaluable cultural heritage far exceeding its economic importance. We used primarily a PCR-based sequencing approach in order to unravel population dynamic responses to environmental stimuli, and we combined it with data from classical cultivation-based microbiology to understand the genomic potential of endophytes and how closely these microbial symbionts resemble pathogens. Through this integrated approach we discovered the first documented interkingdom transfer of a microbial symbiont from man to plants. Eventually, our research effort uncovered the unexpected role played by some plant-dwelling insects in the dispersal of microbial endophytes and in the colonization of axenic plants.