Microorganisms are an integral part of the composition of fruits and vegetables and are found as epiphytes on the surface or as endophytes within tissues. The realization that fruit surfaces harbor beneficial microorganisms fostered the field of biological control using epiphytic microorganisms which led to the development of several commercial biocontrol products. Advances in DNA sequencing and “omics” technologies have enhanced our ability to characterize the diversity and function of microbial communities (microbiome) present in and on plant tissues. Microbiome studies have the potential of providing knowledge that will lead to a fundamental paradigm shift in the way we think about biocontrol strategies, biocontrol products, and postharvest biology, as well as the health attributes of fruits and vegetables. Fruit microbiome research will enhance our understanding of harvested commodities as an ecosystem in which the microbiome plays an essential role in the health and physiology of fruit after it is harvested. Meta-omic (metagenomics, metatranscriptomics, metaproteomics, and metametabolomics) technologies are only beginning to be applied to postharvest studies and will revolutionize our understanding of postharvest biocontrol systems, foodborne pathogens, and postharvest physiology. The role of the microbiome in plant health, productivity, and cultivar development should be considered as much as the plant itself. Plant breeding or genetic modification of plants could be used to intentionally modulate the composition of the microbiome and its function, recruiting disease antagonists and plant-growth promoters that enhance plant health and the quality of the harvested products. Increased knowledge of microbial community systems will lead to the development of natural or synthetic consortia that can be used to prevent postharvest diseases and mitigate physiological disorders in harvested commodities.