question: Entomopathogenic nematodes are parasitic organisms with an exceptional capacity to infect rapidly and efficiently a wide range of insect species. Their distinct pathogenic properties have established entomopathogenic nematodes as supreme biocontrol agents of insects as well as excellent models to simulate and dissect the molecular and physiological bases of conserved strategies employed by parasitic nematodes that cause infectious diseases in humans. The extreme infectivity of entomopathogenic nematodes is due in part to the presence of certain species of Gram-negative bacteria that live in mutualistic symbiosis during the infective juvenile stage, which forms the central part of the nematode life cycle. Both nematodes and their mutualistic bacteria are capable of interfering and undermining several aspects of the insect host innate immune system during the infection process. The mutualistic bacteria are also able to modulate other biological functions in their nematode host including growth, development, and reproduction. In this review, we will focus our attention on the mutualistic relationship between entomopathogenic nematodes and their associated bacteria to discuss the nature and distinct characteristics of the regulatory mechanisms, and their molecular as well as physiological components that control this specific biological partnership.