This paper reviews the limits to exercise imposed by increases in ambient, hypothalamic, and contracting skeletal muscle temperature in humans and horses. Like humans, horses frequently compete in hot environments, yet their high mass-specific rate of heat production and low mass-specific surface area for heat dissipation places them at a great disadvantage compared to humans. Exercise in hot conditions increases the rate of body heat storage and reduces the time required to reach a critical hypothalamic temperature that results in voluntary fatigue. This critical temperature appears to be associated with dysfunction of the brain's motor control centres. The ensuing voluntary cessation of exercise appears to coincide with temperature-induced alterations in skeletal muscle function with increased requirement for anaerobic ATP provision. The duration of exercise that can be performed before this critical temperature is reached can be increased by ingesting fluids, of a volume at least equal to that lost in sweat, within 60 min prior to and during exercise. Emerging research in the area of skeletal muscle heat dissipative mechanisms involves heat-induced increases in muscle sympathetic nerve activity, producing stimulation of CIII and CIV afferent nerve stimulation, and heat-induced release of nitric oxide within skeletal muscle and skin, producing muscle and skin vasodilation.