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Infections caused by drug-resistant pathogens are a global public health problem. The introduction of a new antimicrobial strategy is an unavoidable option for the management of drug-resistant pathogens. Induction of high levels of reactive oxygen species (ROS) by several procedures has been extensively studied for the treatment of infections. In this article, the general aspects of ROS production and the common procedures that exert their antimicrobial effects due to ROS formation are reviewed. ROS generation is the antimicrobial mechanism of nanoparticles, hyperbaric oxygen therapy, medical honey, and photodynamic therapy. In addition, it is an alternative bactericidal mechanism of clinically traditional antibiotics. The development of ROS delivery methods with a desirable selectivity for pathogens without side effects for the host tissue may be a promising approach for the treatment of infections, especially …