Plant growthâpromoting rhizobacteria (PGPR) are diverse groups of plantâassociated microorganisms, which can reduce the severity or incidence of disease during antagonism among bacteria and soilâborne pathogens, as well as by influencing a systemic resistance to elicit defense response in host plants. An amalgamation of various strains of PGPR has improved the efficacy by enhancing the systemic resistance opposed to various pathogens affecting the crop. Many PGPR used with seed treatment causes structural improvement of the cell wall and physiological/biochemical changes leading to the synthesis of proteins, peptides, and chemicals occupied in plant defense mechanisms. The major determinants of PGPRâmediated induced systemic resistance (ISR) are lipopolysaccharides, lipopeptides, siderophores, pyocyanin, antibiotics 2,4âdiacetylphoroglucinol, the volatile 2,3âbutanediol, Nâalkylated benzylamine, and ironâregulated compounds. Many PGPR inoculants have been commercialized and these inoculants consequently aid in the improvement of crop growth yield and provide effective reinforcement to the crop from disease, whereas other inoculants are used as biofertilizers for native as well as crops growing at diverse extreme habitat and exhibit multifunctional plant growthâpromoting attributes. A number of applications of PGPR formulation are needed to maintain the resistance levels in crop plants. Several microarrayâbased studies have been done to identify the genes, which are associated with PGPRâinduced systemic resistance. Identification of these genes associated with ISRâmediating disease suppression and biochemical changes in the crop plant is one of the essential steps in understanding the disease resistance mechanisms in crops. Therefore, in this review, we discuss the PGPRâmediated innovative methods, focusing on the mode of action of compounds authorized that may be significant in the development contributing to enhance plant growth, disease resistance, and serve as an efficient bioinoculants for sustainable agriculture. The review also highlights current research progress in this field with a special emphasis on challenges, limitations, and their environmental and economic advantages.