Nonthermal plasma (NTP) is classified as a particular case of physical radiation type of sterilization. Contrary to conventional sterilization practices (autoclaving, dry heat, and gamma radiation), NTP has several valuable advantages, such as a higher success rate of killing diverse microorganisms with no harmful effects on human tissues, technological flexibility, environmental safety, energy-saving performance, etc. However, the best decontamination results are typically obtained with surface sterilization while microbial cells entrapped inside solid materials or suspended in liquid remain more resistant. This entry covers the methodology of decontamination testing (exposure, recovery of treated cells, plating, and alternative techniques to assess survival rate), factors affecting decontamination (gas composition of NTP, humidity, added oxidants, pH, and physiological state of cells), process kinetics, and underlying destruction mechanisms (direct and indirect effects of NTP, conventional observations and genomic data, NTP as simulator of innate immunity, etc.).