The article discusses the antimicrobial actions of silver nanoparticles (AgNPs) and their mechanisms of action against multidrug-resistant microorganisms. AgNPs exhibit potent antibacterial and antifungal properties due to their ability to adhere to microbial cell surfaces, penetrate cells, generate reactive oxygen species (ROS), and modulate signal transduction pathways. However, their exposure to human cells can induce cytotoxicity, genotoxicity, and inflammatory responses. The physico-chemical properties of AgNPs, such as size, shape, surface charge, and concentration, significantly influence their antimicrobial efficacy. The article also highlights the need for further research to engineer AgNPs to enhance their efficacy, stability, specificity, biosafety, and biocompatibility. Additionally, it reviews the challenges and emerging efforts in safe therapeutic and drug delivery applications of AgNPs.The article discusses the antimicrobial actions of silver nanoparticles (AgNPs) and their mechanisms of action against multidrug-resistant microorganisms. AgNPs exhibit potent antibacterial and antifungal properties due to their ability to adhere to microbial cell surfaces, penetrate cells, generate reactive oxygen species (ROS), and modulate signal transduction pathways. However, their exposure to human cells can induce cytotoxicity, genotoxicity, and inflammatory responses. The physico-chemical properties of AgNPs, such as size, shape, surface charge, and concentration, significantly influence their antimicrobial efficacy. The article also highlights the need for further research to engineer AgNPs to enhance their efficacy, stability, specificity, biosafety, and biocompatibility. Additionally, it reviews the challenges and emerging efforts in safe therapeutic and drug delivery applications of AgNPs.