Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed. Keywords: antimicrobial activity, nanoparticles, oxidative stress, antimicrobial resistance Bacterial infections are a major cause of chronic infections and mortality. Antibiotics have been the preferred treatment method for bacterial infections because of their cost-effectiveness and powerful outcomes. However, several studies have provided direct evidence that the widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains. In fact, super-bacteria, which are resistant to nearly all antibiotics, have recently developed due to abuse of antibiotics. Studies have shown that these bacteria carry a super-resistance gene called NDM-1. The major groups of antibiotics that are currently in use have three bacterial targets: the cell wall synthesis, translational machinery, and DNA replication machinery. Unfortunately, bacterial resistance can develop against each of these modes of action. The mechanisms of resistance include expression of enzymes that modify or degrade antibiotics, such as β-lactamases and aminoglycosides, modification of cell components, such as the cell wall in vancomycin resistance and ribosomes in tetracycline resistance, and expression of efflux pumps, which provide simultaneous resistance against numerous antibiotics. Most of the antibiotic resistance mechanisms are irrelevant for nanoparticles (NPs) because the mode of action of NPs is direct contact with the bacterial cell wall, without the need to penetrate the cell; this raises the hope that NPs would be less prone to promoting resistance in bacteria than antibiotics. Therefore, attention has been focused on new and exciting NP-based materials with antibacterial activity. Most bacteria exist in the form of a biofilm, which often contains diverse species that interact with each other and their environment. Biofilms are specifically microbial aggregates that rely on a solid surface and extracellular products, such as extracellular polymeric substances (EPSs). Bacteria move reversibly onto the surface, but the expression of EPSs renders the attachment irreversible. Once the bacteria are settled, synthesis of the bacterial flagellum is inhibited, and the bacteria multiply rapidly, resulting in the development of a mature bioNanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed. Keywords: antimicrobial activity, nanoparticles, oxidative stress, antimicrobial resistance Bacterial infections are a major cause of chronic infections and mortality. Antibiotics have been the preferred treatment method for bacterial infections because of their cost-effectiveness and powerful outcomes. However, several studies have provided direct evidence that the widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains. In fact, super-bacteria, which are resistant to nearly all antibiotics, have recently developed due to abuse of antibiotics. Studies have shown that these bacteria carry a super-resistance gene called NDM-1. The major groups of antibiotics that are currently in use have three bacterial targets: the cell wall synthesis, translational machinery, and DNA replication machinery. Unfortunately, bacterial resistance can develop against each of these modes of action. The mechanisms of resistance include expression of enzymes that modify or degrade antibiotics, such as β-lactamases and aminoglycosides, modification of cell components, such as the cell wall in vancomycin resistance and ribosomes in tetracycline resistance, and expression of efflux pumps, which provide simultaneous resistance against numerous antibiotics. Most of the antibiotic resistance mechanisms are irrelevant for nanoparticles (NPs) because the mode of action of NPs is direct contact with the bacterial cell wall, without the need to penetrate the cell; this raises the hope that NPs would be less prone to promoting resistance in bacteria than antibiotics. Therefore, attention has been focused on new and exciting NP-based materials with antibacterial activity. Most bacteria exist in the form of a biofilm, which often contains diverse species that interact with each other and their environment. Biofilms are specifically microbial aggregates that rely on a solid surface and extracellular products, such as extracellular polymeric substances (EPSs). Bacteria move reversibly onto the surface, but the expression of EPSs renders the attachment irreversible. Once the bacteria are settled, synthesis of the bacterial flagellum is inhibited, and the bacteria multiply rapidly, resulting in the development of a mature bio