There is growing body of evidence linking the cellular response to heat stress with the response of the immune system to cancer. The anti-tumor immune response can be markedly enhanced by treatment with hyperthermia particularly in the fever range. In addition, the heat shock proteins (hsp) which are produced in abundant quantities in cells exposed to heat are potent immune modulators and can lead to stimulation of both the innate and adaptive immune responses to tumors. Immunostimulation by hyperthermia involves both direct effects of heat on the behavior of immune cells as well as indirect effects mediated through hsp release. In addition, the hsp can be deployed as components of antitumor vaccines in protocols that do not include hyperthermia. Understanding these process may permit the effective deployment of hyperthermia and hsp based vaccines in tumor treatment.