<p>Infectious diseases still pose one of the leading causes of morbidity and mortality in the world, and the problem of antimicrobial resistance is becoming more and more dangerous to the health of global populations. Multidrug-resistant (MDR) bacteria have emerged rapidly, and this has become a cause of concern among international health organizations and government agencies such as the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). The scarcity of the emergence of new antimicrobial agents and the decreasing efficacy of the current antibiotics predominantly cause this crisis. The mechanisms of bacterial resistance are varied and some of them include enzyme inactivation, low-membrane permeability, target site protection or alteration, target overexpression, structural changes of the enzymes or cellular structures, and increased efflux through overexpressed efflux pumps. Due to their distinctive physicochemical characteristics, nanoparticles have become the potentially promising antimicrobial agents that can either work alone or serve as the carriers of antimicrobial agents without necessarily undergoing the standard mechanisms of resistance. Nanoparticle categories, such as metallic, organic, carbon-based, and hybrid systems have proved to be very effective with regard to antibacterial activity against MDR pathogens. Moreover, nanoparticles are under investigation in combination with plant-derived antimicrobials to improve the ability and minimize the toxicity. Recent methods of using nanoparticles are biofilm disruption, quorum sensing, plasmid eradication, efflux pump, and synergist antimicrobial combinations. Irrespective of these improvements, there are safety, biocompatibility, scalability, and environmental impact issues. This review comprises newly developed developments in nanoparticle-based approaches to addressing drug-resistant bacteria and addresses their clinical translation possibilities.</p>