Exemplary methods and systems for killing or deactivating spores include applying a fluid to a surface containing a spore; and applying direct or indirect plasma to the surface for a period of time. In some embodiments, the fluid includes water. In some embodiments, the spore is Clostridium difficile and in some is Bacillus Anthracis. In some embodiments, the fluid is in the form of a vapor, a fog, a spray, a mist or an aerosol, which may be activated prior to or after applying the fluid to a surface. In some embodiments, peroxynitrite is created in the fluid during the method. Another exemplary embodiment of killing or deactivating a spore includes treating spores with direct plasma or indirect plasma for a period of time and applying an antimicrobial to the spores. In some embodiments, the antimicrobial is an alcohol, a bleach or an alcohol-based sanitizer.