Plants naturally harbours a complex microbial ecosystem or plant microbiome, as neutral, beneficial or pathogens microorganisms, that are in a close interaction with the plant. The balance of these interactions is a key element for plant health, plant growth and productivity although several factors as ecological and environmental factors represents important drivers of the microorganism’s community. Herein, a review on plant microbiome is presented, and the case study of Vitis vinifera (grapevine) is presented as an example of the application of the study of a woody plant microbiome. Overall, new ecologically and sustainable strategies for agriculture are needed. The exploitation of the natural microbiome associated with plants and the identification of novel potential strains with plant benefits and biocontrol potential represent a challenge and a technological development for crops protection.