This review has covered the pertinent literature concerning the teratogenic effects of hyperthermia in man and experimental animals. This is the first teratogen that was initially discovered in animals and then subsequently found to be a cause for concern in humans when similar patterns of defects were observed. Hyperthermia is a physical agent with a dose-response curve for abortions and malformations, but these effects can be mitigated in some circumstances by the heat shock response (HSR). We have reviewed the known functions of HSR and provided some insight into why embryos have some protection following an initial dose of heat, if it is sufficient to initiate the response. Thus, by reviewing the effects of hyperthermia in experimental animals, as well as malformative and protective mechanisms of teratogenesis, we have attempted to understand the effects of human hyperthermia teratogenesis.