Irreversible thermal alterations in tissues result from denaturation of native state tissue enzymes, proteins, and related structures, such as cell membranes, micro tubules, and the like. Mathematical description of these processes, while somewhat cumbersome, yields valuable insight into experimentally observed tissue changes and is a worthwhile undertaking. Predictions of temperature alone are just not adequate since the time of exposure is a dening parameter: hour-long hyperthermia treatments at moderate temperatures exhibit dierent thermal alteration processes than minutes-long treatments at higher temperatures in ablation procedures. is chapter reviews thermal damage processes in tissues, their physical-chemical thermodynamic governing relations, and useful approximations that have been used to describe them. Specic modeling approaches that have proven useful are also discussed.