The use of heat to inactivate food-borne pathogens is a critical control point and the most common means of assuring the microbiological safety of processed foods. A key to optimization of the heating step is defining the target pathogen's heat resistance. Heat resistance of microorganisms can vary depending on the species and strain of bacteria, food composition, physiological state of microbial cells or spores, and recovery conditions (type of media, temperature, atmosphere and time of incubation) for the detection of survivors. Cells grown at higher temperatures or exposed to sub-lethal heat shock, and those growing in a minimal, or fat-rich medium, are more heat resistant. Cells attached to meat surfaces, stainless steel or glass surfaces are more heat resistant than those that are unattached and dispersed throughout in foods. Recovery under anaerobic conditions, at lower temperatures and on non-selective, rich media rather than on selective media, enhance recovery of injured cells. Food characteristics leading to increased heat resistance of an organism include reduced water activity and the presence of carbohydrates, lipids, proteins, salt, etc. Quantitative knowledge of the factors in muscle foods that interact and influence the inactivation kinetics are required to estimate accurately how a particular pathogen is likely to behave in a specific food. There is a need for a better understanding of how the interactions among preservation variables can be used for predicting the safety of minimally processed, ready-to-eat meat products. The effects and interactions of temperature, pH, sodium chloride content, and sodium pyrophosphate concentration are among the variables that were considered when attempting to assess the heat-inactivation kinetics of Escherichia coli O157:H7, Listeria monocytogenes, and spores of non-proteolytic Clostridium botulinum. Incorporation of these multiple barriers increased the sensitivity of pathogens to heat, thereby reducing heat requirements and ensuring the safety of ready-to-eat food products. For example, C. botulinum D-values at 75 degrees C in ground turkey supplemented with 1% salt and 0.1% phosphate at pH 5.5 and 6.25 were 36.1 and 39.1, respectively. When ground turkey contained 2% salt and 0.2% phosphate, the observed D-values in turkey at pH 5.5 and 6.25 decreased by 42.1% and 22.1%, respectively. Confidence intervals were developed to allow food processors to know the expected heat resistance of the pathogens. The future of thermal-death determinations of bacteria will likely rely on predictive thermal inactivation kinetics modeling. Complex multifactorial experiments and analysis to quantify the effects and interactions of additional intrinsic and extrinsic factors and development of "enhanced" predictive models are warranted to ensure the microbiological safety of thermally processed foods.