Nowadays, population growth, the global temperature increase, and the appearance of emerging diseases in important crops generate uncertainty regarding world food security. The use of agrochemicals has been the “go-to” solution for the control of phytopathogenic microorganisms, such as Magnaporte oryzae, causing blast disease in rice and other cereals; Botrytis cinerea, causing gray mold in over 500 plant species; and Puccinia spp., causing rust in cereals. However, their excessive use has harmed human health, as well as ecosystems (contaminating water, and contributing to soil degradation); besides, phytopathogens can develop resistance to them. The inoculation of plant growth-promoting microorganisms (PGPMs) to crops is a sustainable strategy for increasing the yield and quality of crops and mitigating biotic stresses. Likewise, PGPMs, such as Pseudomonas, Bacillus, and Trichoderma, can trigger a series of signals and reactions in the plant that lead to the induction of systemic resistance, a mechanism by which plants react to microorganism stimulation by activating their defense system, resulting in protection against future pathogen attack. These plant defense mechanisms help to mitigate biotic stresses that threaten global food security. Thus, the study of these mechanisms at molecular, transcriptomic, and metabolomic levels is indispensable to elucidate how stresses affect globally important crops.