Despite the constant development of novel thermal and nonthermal technologies, knowledge on the mechanisms of microbial inactivation is still very limited. Technologies such as high pressure, ultraviolet light, pulsed light, ozone, power ultrasound and cold plasma (advanced oxidation processes) have shown promising results for inactivation of micro-organisms. The efficacy of inactivation is greatly enhanced by combination of conventional (thermal) with nonthermal, or nonthermal with another nonthermal technique. The key advantages offered by nonthermal processes in combination with sublethal mild temperature (<60°C) can inactivate micro-organisms synergistically. Microbial cells, when subjected to environmental stress, can be either injured or killed. In some cases, cells are believed to be inactivated, but may only be sublethally injured leading to their recovery or, if the injury is lethal, to cell death. It is of major concern when micro-organisms adapt to stress during processing. If the cells adapt to a certain stress, it is associated with enhanced protection against other subsequent stresses. One of the most striking problems during inactivation of micro-organisms is spores. They are the most resistant form of microbial cells and relatively difficult to inactivate by common inactivation techniques, including heat sterilization, radiation, oxidizing agents and various chemicals. Various novel nonthermal processing technologies, alone or in combination, have shown potential for vegetative cells and spores inactivation. Predictive microbiology can be used to focus on the quantitative description of the microbial behaviour in food products, for a given set of environmental conditions.