Acclimation of domestic animals to high environmental temperature typically results in lower production as animals lower their metabolic rate and feed intake to accommodate the increased heat load. Ideally, one would like to simultaneously select for increased production and thermal resistance to increased thermal load. This will require simultaneous identification and selection for improved heat dissipation and production mechanisms. Rate of genetic progress in domestic animal breeding programs is driven by 3 factors; accuracy of markers for phenotypic traits, intensity of marker use and generation interval. Improved tools in molecular analysis of gene expression will permit improvement in the accuracy and intensity of use of genetic markers. New techniques in reproductive biology will permit reduction of generation interval. Collectively these new techniques offer real opportunity to improve tolerance for environmental heat stress in domestic animals. Presently, genetic markers for phenotypic traits do not correspond to the coding regions for the genes of interest. They are located close to loci of traits of interest but lose their value over time due to genetic recombination. Ideally, genetic markers should identify the exact location of the gene of interest. Thus, identifying these genes is a major objective of any breeding program. Combining use of consomic lines of rats with single gene deletions and gene expression microarrays that permit evaluation of expression levels of thousands of genes at a time will rapidly increase knowledge of genes associated with tolerance or sensitivity to environmental heat stress. Targets of potential genetic manipulation would include increased efficiency and capacity of thermal effectors and delayed onset of temperature threshold for thermal injury. For example, constitutive elevation of heat shock protein gene expression has been shown to be cytoprotective against thermal injury in rats. This approach has not yet been tested in domestic animals. Likewise, treatment of lactating dairy cows with bovine somatotropin has been shown to increase evaporative heat loss capacity. Understanding the molecular basis for the increased evaporative heat loss capability offers new opportunities for increasing thermal tolerance of cattle in warm climates. Finally, unraveling molecular changes associated with seasonal adaptation will offer new insights into selecting domestic animals for thermal tolerance