1. Contracting skeletal muscle is able to use a number of intra- and extramuscular substrates to generate ATP during exercise. These include creatine phosphate (CP), muscle glycogen, blood-borne glucose, lactate and free fatty acids (FFA), derived from either adipose tissue or intramuscular triglyceride stores. 2. During high-intensity short-duration exercise, CP degradation and the breakdown of muscle glycogen to lactate are the major energy yielding pathways, although oxidative metabolism can make a significant contribution. The 'anaerobic' substrates are also important fuels during the transition from rest to steady state exercise. 3. The oxidative metabolism of carbohydrate and lipid supplies most, if not all, of the ATP during prolonged submaximal exercise. Muscle glycogen, blood glucose and FFA are the key fuels. The relative importance of the various substrates for exercise metabolism is primarily determined by exercise intensity and duration, although training status, dietary manipulation and environmental factors can modify the metabolic response to exercise.