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The thermal processing of food relies heavily on determining the right time and temperature regime required to inactivate bacterial contaminants to an acceptable limit. To design a thermal processing regime with an accurate time and temperature combination, the D-values of targeted microorganisms are either referred to or estimated. The D-value is the time required at a given temperature to reduce the bacterial population by 90%. The D-value can vary depending on various factors such as the food matrix, the bacterial strain, and the conditions it has previously been exposed to; the intrinsic properties of the food (moisture, water activity, fat content, and pH); the method used to expose the microorganism to the thermal treatment either at the laboratory or commercial scale; the approach used to estimate the number of survivors; and the statistical model used for the analysis of the data. This review focused on <i>Bacillus cereus</i>, <i>Cronobacter sakazakii</i>, <i>Escherichia coli</i>, <i>Listeria monocytogenes</i>, and <i>Clostridium perfringens</i> owing to their pathogenicity and the availability of publications on their thermal resistance. The literature indicates a significant variation in D-values reported for the same strain, and it is concluded that when designing thermal processing regimes, the impact of multiple factors on the D-values of a specific microorganism needs to be considered. Further, owing to the complexity of the interactions involved, the effectiveness of regimes derived laboratory data must be confirmed within industrial food processing settings.