The limits to endurance exercise and the causes of muscle fatigue are not entirely understood. Recently basic physiology has focussed much attention on the role of elevated temperatures and reactive oxygen species (ROS). Exercise is commonly associated with an increase in temperature of up to 6 °C in the working muscles. Increases of one to two degrees in muscle temperature are generally accepted as being beneficial to performance, but further increases in core and muscle temperature are considered to accelerate the development of fatigue. Increased muscle temperature is also accompanied by increased production of ROS. I will discuss the effects of ROS on single intact slow- and fast-twitch skeletal muscle fibres during the development of fatigue and in particular their relatively specific effects on the contractile proteins and the calcium release channel.