The relationship between dietary intake and skeletal-muscle exercise metabolism is central to the interests of exercise physiologists. This area has been examined experimentally for over 100 years. Classic studies with male subjects demonstrated the importance of dietary CHO in maximizing muscle and liver glycogen stores in an attempt to optimize exercise performance. CHO becomes the predominant fuel for exercise at power outputs above 50-60% Vo2max and its availability limits prolonged aerobic exercise at intensities corresponding to 65-85% VO2max. Recent information suggests that female subjects are less able to maximize muscle glycogen stores through dietary means. Contemporary studies have documented in more detail the greater reliance on CHO metabolism following a high-CHO-low-fat and -protein diet and the greater reliance on fat metabolism following a low-CHO-high-fat and protein diet. More emphasis on documenting key enzymic changes in the energy-producing pathways and transport proteins has appeared. However, very little is known regarding the mechanisms that induce these changes over the short or long term in human skeletal muscle. For example, the central role of PDH activity in the selection of intramuscular fuel during exercise and the role of carnitine palmitoyltransferase 1 in the entry of NEFA into the mitochondria, and the effects of diet on these enzymes has received little attention to date. Many research studies have examined extreme diet variations (% total energy; > 85% CHO v. < 5-10% CHO) for short periods of time in an attempt to maximize diet-induced alterations and study the mechanisms responsible for the changes. However, future studies will need to examine less-severe diet alterations for longer periods of time that more accurately reflect what the normal population might experience, such as a diet containing (% total energy) 60 fat, 20 CHO, 20 protein or the recently popular diet with (% total energy) 30 fat, 40 CHO, 30 protein.