Plants have developed numerous pre-existing and inducible defense mechanisms to combat the various pathogenic threats to which they are exposed. These defense mechanisms are supported by biocontrol agents, including fungi, antagonistic bacteria, and plant growth-promoting rhizobacteria (PGPR). PGPR enhance plant growth and resistance through multiple mechanisms: eliciting induction of systemic resistance (ISR) or systemic acquired resistance (SAR), improving food production, synthesizing growth promoters, inhibiting the growth of phytopathogens, emitting volatile compounds, and secreting antimicrobial metabolites. Trichoderma harzianum, a nursery-grown fungus, controls phytopathogenic fungi by activating plant-made antimicrobial compounds, antibiosis, and cell wall-degrading enzymes. Only five PGPRs have had their genomes fully sequenced: four strains of Pseudomonas fluorescens and Agrobacterium radiobacter K84. In biocontrol research, proteomics is a game-changing technology that provides insight into the relationships among plants, diseases, and biocontrol agents. Advanced methods such as globular and organellar proteomics, which are focused on deep analysis of the plant proteome show how biocontrol treatments can change the defense mechanisms and metabolic processes in plants. These findings are invaluable, as they shed light on the molecular and metabolic alterations occurring in plants with the support of those beneficial microbes. Taken together, these recent advancements may pave the way to greater sustainability and efficacy in plant disease control. At the same time, it can offer a new look at plant defense. This chapter develops the manner through which recent trends in proteomics could impact plant defense mechanisms.