Nowadays non-thermal plasma is considered functionally, energetically and ecologically as the most efficient tool for pathogenic bacteria inactivation - due to high chemical activity of low-temperature energy efficient plasma, short-time treatment and minimal thermolabile materials’ destruction. Non-thermal plasma is essentially non-equilibrium one because the ion (and neutrals) temperature remains low, electron temperature being high. The grade of ionization is proportional to the electron temperature and defines chemical activity of plasma. As a result, “cold” plasma is energetically the most efficient instrument for the catalytic acceleration of chemical reactions. It could be used for ecologically pure surface treatment of thermo-labile materials (antimicrobial food processing, sterilization of medical instruments, self-decontaminating filters, during medical invasions etc.).   The thermodynamic approach is elaborated for the optimization of sterilization processes. Optimal plasma composition for sterilization is proposed and investigated.  Microwaves are one of the best methods of obtaining dense active cold plasma: the higher is the frequency and applied power, the higher is the grade of non-equilibrium and plasma density [1]. For the most typical microwave discharges plasma density (i.e., the concentration of free electrons) is rather large, respectively electron plasma frequency is sufficiently high and surpasses the cyclic frequency of microwave generation. So, the frequency of the electromagnetic field remains smaller than the plasma frequency, and this corresponds to the condition of effective (high) absorption of microwave energy by plasma. Also should be mentioned the advantages of microwave discharge plasma - as electrodeless and which could be easily maintained at relatively high (inclusively, atmospheric) pressure.   We demonstrated that for the generation of the non-equilibrium (non-thermal) plasma it is not obligatory to use harmonic high frequency oscillations (impulses of, or continuous). The same effect can be obtained as a result of application of the short (nano- and picosecond) high voltage impulses. In this case plasma parameters can be controlled through the amplitude, duration and duty ratio of impulses. The respective simplification of the installation - due to MW components elimination - illustrates Fig.1.  We consider that plasma chemical reaction of oxidation is the best method for irreversible sterilization, without any chance of eventual “adaptation” for microorganisms: being the shortest way of obtaining sterility, it transforms finally the organic compounds in gas phase.  Most of the physical methods of sterilization (heating, high pressure, US, UV and other radiations) provoke “endothermic” structural destructions, and there always remains a certain possibility of reparation, or even creation of new mutations - viable (virulent) forms. So, it is indicated to use the above mentioned methods only as a supplement, together with non-equilibrium plasma oxidation.