Increasing population, changing climatic conditions and crop diseases are serious threats to agriculture which should be encountered in sustainable ways. Increased productivity and protection from pathogens by using chemical fertilizers and pesticides, although is a feasible approach, causes serious problems for sustainable agriculture. In such a scenario, the usage of plant growth-promoting rhizobacteria (PGPR) can be considered a feasible, economical and environment-friendly approach to promote plant growth, increase productivity and control plant diseases from pathogens. Many PGPR are known to activate immune responses in plants by producing pathogen-antagonizing compounds to suppress diseases and induce systemic resistance against a broad spectrum of pathogenic microorganisms. The usage of PGPR with biological control activities is proven to be an efficient strategy to combat plant diseases and increase plant growth and productivity. The PGPR that can elicit systemic resistance in plants show changes at morphological, physiological, biochemical and molecular levels in host plants. In this context, the perception of microbial signals by host plants, the signaling pathways that are involved in the response and the PGPR-induced systemic resistance against pathogens are actively studied and reviewed by many researchers. In the current chapter, the functional mechanisms of PGPR that help plants by multifaceted contributions toward growth, development and protection from pathogenic microorganisms will be discussed.