Currently, agriculture is at a crossroads similar to that experienced at the beginning of the last century. The growing need to supply food to global markets and the incipient climate is expected to jeopardize the current agricultural systems. This situation requires a rethinking of agricultural production systems, and it is clearly necessary to incorporate new tools and agronomic practices that improve efficiency and sustainability. A key factor can be identified in using resources or the competition of crops to resist biotic and abiotic stresses. Plant growth-promoting bacteria (PGPB) are of outstanding utility due to the multiple mechanisms with which they influence plant development. It is fundamental, at these crossroads, to delve deeper into the mechanisms by which PGPB can improve the development of plants in the soil at the phenotypic level. Biochemical methods, incorporating genomic, transcriptomic, proteomic, and metabolomic analyses, can help us understand these interactions. In addition, omics techniques will make it possible to create a complete and complex vision using big data technologies, spurring new strategies to achieve an agriculture with a greater degree of integration of the environment, and greater efficiency of production with reduced risk to human.