Antimicrobial resistance has become a severe problem for health systems worldwide, and counteractions are challenging because of the lack of interest of pharmaceutical companies in generating new and effective antimicrobial drugs. Selenium nanoparticles have attracted considerable interest in treating bacteria, fungi, parasites, and viruses of clinical importance due to their high therapeutic efficacy and almost zero generation of adverse effects. Some studies have revealed that the antimicrobial activity of these nanoparticles is due to the generation of reactive oxygen species, but more studies are needed to clarify their antimicrobial mechanisms. Other studies show that their antimicrobial activity is increased when the surface of the nanoparticles is functionalized with some biomolecules or when their surface carries a specific drug. This review addresses the existing background on the antimicrobial potential offered by selenium nanoparticles against viruses, bacteria, fungi, and parasites of clinical importance.