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Reactive oxygen species (ROS) are essential participants of various innate immune cell responses against microorganisms and are also involved in many cellular regulatory pathways. It was believed that the main pool of ROS in the innate immune cells is generated by the NADPH oxidase enzymatic complex. However, it was discovered recently that mitochondrial ROS (mtROS) are equally important for the functioning of the immune system. mtROS play an important role in the development of the antimicrobial innate immune responses. The present work summarizes the most recent data on the role of mtROS in the antibacterial immunity. The principles of mtROS formation and possible mechanisms of their generation under the activation of innate immunity are highlighted in this work. We also speculate on the possibilities of using activators of mtROS production in clinical practice.