Fat and carbohydrate are the primary fuel sources for mitochondrial ATP production in human skeletal muscle during endurance exercise. However, fat exhibits a relatively low maximal rate of oxidation in vivo, which begins to decline at around 65% of maximal oxygen consumption (VO₂max) when muscle glycogen becomes the major fuel. It is thought that if the rate of fat oxidation during endurance exercise could be augmented, then muscle glycogen depletion could be delayed and endurance improved. The purpose of the present review is to outline the role of carnitine in skeletal muscle fat oxidation and how this is influenced by the role of carnitine in muscle carbohydrate oxidation. Specifically, it will propose a novel hypothesis outlining how muscle free carnitine availability is limiting to the rate of fat oxidation. The review will also highlight recent research demonstrating that increasing the muscle carnitine pool in humans can have a significant impact upon both fat and carbohydrate metabolism during endurance exercise which is dependent upon the intensity of exercise performed.