Plants are an intrinsic part of the soil community and the “one health concept” considers that human health is intimately connected to the health of animals, plants, and microbial environments. Plant-microbe interactions are a cornerstone of one health, the soil microbiome being comprised of a diverse range of organisms, interacts in the rhizosphere through continuous molecular communications. Soils are a source and reservoir of pathogens, as well as beneficial microorganisms. Hence, the molecular dialogue at the rhizosphere interface is crucial not only for successful plant-microbe interactions but also for crop resilience and stress tolerance. The plant-microbe continuum forms a network of underground “nutrient highways” that benefit both plant and microbial communities. It also serves as a significant sink for atmospheric CO ₂. While microbial diversity is generally positively associated with one health, the host range of beneficial microbes currently limits their successful exploitation with a wide range of microbial communities. We consider the possibility of increasing the host range of beneficial microbes, including arbuscular mycorrhiza fungi (AMF) and rhizobia, and how current genetic incompatibility and/or activation of robust plant defenses, can be overcome while accepting that significant challenges exist in translating laboratory findings into the field. We consider why AMF inoculants and plant growth-promoting microbes are not always beneficial under field conditions and suggest possible approaches for tailoring plant-microbe interactions to assist plant breeding efforts in crop resilience.