High-pressure processing (HPP) is a noveltechnology for the production of minimally processed foodproducts with better retention of the natural aroma, freshliketaste, additive-free, stable, convenient to use. In thisregard safety of products by microbial inactivation is likelyto become an important focus for food technologists fromthe research and industrial field. High pressure inducesconformational changes in the cell membranes, cell morphology. It perturbs biochemical reactions, as well as thegenetic mechanism of the microorganisms, thus ensures thereduction in the microbial count. Keeping in view thecommercial demand of HPP products, the scientific literatureavailable on the mechanism of inactivation by highpressure and intrinsic and extrinsic factors affecting theefficiency of HPP are systematically and critically analyzedin this review to develop a clear understanding of theseissues. Modeling applied to study the microbial inactivationkinetics by HPP is also discussed for the benefit ofinterested readers.