Much of the effect of heat stress on establishment and maintenance of pregnancy involves changes in ovarian function and embryonic development that reduce the competence of the oocyte to be fertilized and the resultant embryo to develop. There are three possible therapeutic approaches to manipulate the connection between hyperthermia and cellular responses to elevated temperature to improve fertility during heat stress. Embryo transfer is based on the idea that 1) most effects of heat stress on fertility involve actions during folliculogenesis or on cleavage-stage embryos and 2) the embryo has acquired resistance to elevated temperature by the time it is transferred at the morula or blastocyst stage. The mechanisms for acquisition of thermotolerance involve changes in production of reactive oxygen species in response to heat shock as well as accumulation of antioxidants in the embryo. Synthesis of heat shock proteins may not be the controlling factor for acquisition of thermotolerance because transcript abundance for HSPA1A and HSP90AA1 is higher for the two-cell embryo than morula. Involvement of reactive oxygen species in actions of elevated temperature on embryo survival is indicative that provision of antioxidants to heat-stressed cows could improve fertility. More work is needed but there are indications that pregnancy rates can be improved by feeding supplemental β-carotene or administration of melatonin implants. It is also evident that there are genes that control thermotolerance at the cellular level. Brahman, Nelore and Romosinuano embryos have increased resistance to heat shock as compared to Holstein or Angus embryos. Mutations in the gene for heat shock protein 70 that control resistance of cells to heat shock have been identified in Holsteins. Selection for the desirable alleles of genes conferring cellular thermotolerance could lead to development of strains of cattle whose fertility is resistant to disruption by heat stress. Pursuing these and other therapeutic approaches for reducing consequences of heat stress for livestock species should be a priority because of the prospects for continuing global climate change.