During their separate evolution from Bos taurus, zebu cattle (Bos indicus) have acquired genes that confer thermotolerance at the physiological and cellular levels. Cattle from zebu breeds are better able to regulate body temperature in response to heat stress than are cattle from a variety of B. taurus breeds of European origin. Moreover, exposure to elevated temperature has less deleterious effects on cells from zebu cattle than on cells from European breeds. Superior ability for regulation of body temperature during heat stress is the result of lower metabolic rates as well as increased capacity for heat loss. As compared to European breeds, tissue resistance to heat flow from the body core to the skin is lower for zebu cattle while sweat glands are larger. Properties of the hair coat in zebu cattle enhance conductive and convective heat loss and reduce absorption of solar radiation. At the cellular level, genetic adaptations to resist deleterious effects of elevated temperature result in preimplantation embryos from zebu being less likely to be inhibited in development by elevated temperature than are embryos from European breeds. The zebu genotype has been utilized in crossbreeding systems to develop cattle for beef and dairy production systems in hot climates but success has been limited by other unfavorable genetic characteristics of these cattle. An alternative scheme is to incorporate specific thermotolerance genes from zebu cattle into European breeds while avoiding undesirable genes. Once specific genes responsible for thermotolerance in zebu have been identified or mapped, breeding strategies such as marker-assisted selection and transgenics can be applied to further the exploitation of the zebu genotype for cattle production systems.