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Environment friendly control of plant disease is an emerging need for agriculture in the twenty‐first century. Biological control using antimicrobial producing rhizobacteria to suppress plant diseases and promote plant health offers a powerful alternative to the use of synthetic chemicals. Many studies have been conducted to identify the specific traits by which plant growth‐promoting rhizobacteria (PGPR) promote plant growth. Most of these studies were limited to examining just one or two of these traits. The plant growth‐promoting rhizobacteria produce a wide variety of antimicrobial compounds against pathogens. The addition of antagonistic antimicrobial producing bacterial strains, either individual or as mixture in combination with fungicide, significantly decreased the plant disease stress. A single PGPR strain can produce different kinds of antimicrobial defense compounds to compete pathogens. A biocontrol agent possessing multimechanism systems of defense can antagonize pathogens in a better way. This research chapter highlights the current advancements about plant‐PGPR interactions focusing on the principles and defensive mechanisms of PGPR during disease stress conditions and their potential use for the biocontrol of plant diseases. The integrated use of genetic, molecular, and ecological approaches will form the basis for significant future advances in biocontrol research against plant diseases.