Despite being clinically used for over a century, the benefits of silver nanoparticles are perennially under debate and dispute. In the last two decades, a revived interest in their therapeutic applications has resulted in a few new formulations transitioning into clinical trials. These metal nanomedicines are used in concrete applications that are defined by the physicochemical and biological features of the silver nanoconstructs, as well as their biodistribution profiles. Examples of these applications are topical antibacterial and antiviral therapies and wound healing, as these avoid concerns regarding the long-term accumulation of the nanomedicines in fenestrated organs after intravenous administration. Here, we discuss the current landscape of silver nanoparticles, and critically analyze the characteristics that endowed their transition and use in clinical settings.