Induced systemic resistance (ISR) is a defense mechanism activated by beneficial microbes in the rhizosphere, enhancing plant resistance to pathogens and herbivores. This review discusses the molecular processes involved in ISR, focusing on signaling pathways and the role of the root-specific transcription factor MYB72. ISR is triggered by beneficial microbes such as Pseudomonas, Bacillus, Trichoderma, and mycorrhizal fungi, which sensitize the plant immune system without directly activating costly defenses. Key signaling molecules include phytohormones like salicylic acid (SA), jasmonic acid (JA), and ethylene (ET), which regulate ISR. MYB72 is crucial for the onset of ISR and is highly expressed in root epidermis and cortical cells upon colonization by ISR-inducing microbes. ISR is also influenced by iron homeostasis, as MYB72 is induced under iron-limited conditions. The review highlights the ecological function of ISR-inducing microbes in the root microbiome and the importance of understanding ISR signaling for improving plant health and resilience.Induced systemic resistance (ISR) is a defense mechanism activated by beneficial microbes in the rhizosphere, enhancing plant resistance to pathogens and herbivores. This review discusses the molecular processes involved in ISR, focusing on signaling pathways and the role of the root-specific transcription factor MYB72. ISR is triggered by beneficial microbes such as Pseudomonas, Bacillus, Trichoderma, and mycorrhizal fungi, which sensitize the plant immune system without directly activating costly defenses. Key signaling molecules include phytohormones like salicylic acid (SA), jasmonic acid (JA), and ethylene (ET), which regulate ISR. MYB72 is crucial for the onset of ISR and is highly expressed in root epidermis and cortical cells upon colonization by ISR-inducing microbes. ISR is also influenced by iron homeostasis, as MYB72 is induced under iron-limited conditions. The review highlights the ecological function of ISR-inducing microbes in the root microbiome and the importance of understanding ISR signaling for improving plant health and resilience.