KEY POINTSSustained production of muscular force during exercise depends on the generation of chemical energy (ATP) by nonoxidative (anaerobic) and oxidative ( aerobic) metabolism. Fatigue develops when the compounds needed to produce ATP are depleted or whe n by-products of metabolism accumulate in muscle. These metabolic changes can cause fatigue by acting on nerve processes that a ctivate muscles. Both central and peripheral nervous systems may be impaired. Reductions in muscle levels of ATP, phosphocreatine, and glycogen, and low bl ood glucose availability can impair skeletal muscle performance. Low blood gluco se can also adversely affect central nervous system function. Increases in intramuscular levels of magnesium, ADP, inorganic phosphate, hyd rogen ion, and reactive oxygen species can impair muscle function. Increased amm onia and hyperthermia can also contribute to fatigue, probably via effects on th e central nervous system. Appropriate training programs and nutritional interventions enhance fatigue r esistance and exercise performance by improving the ability of the muscles to su stain ATP production. KEY POINTSSustained production of muscular force during exercise depends on the generation of chemical energy (ATP) by nonoxidative (anaerobic) and oxidative (aerobic) metabolism. Fatigue develops when the compounds needed to produce ATP are depleted or whe n by-products metabolismThese metabolic changes can cause fatigue by acting on nerve processes that a ctivate muscles. Both central and peripheral nervous systems may be impaired.  Reductions in muscle levels of ATP, phosphocreatine, and glycogen, and low bl ood Glucose can can impair skeletal muscle performance. Low blood gluco se can also adversely affect central nervous system function. Increases in intramuscular levels of magnesium, ADP, inorganic phosphate, hyd rogen ion, and reactive oxygen species can impair muscle function. and hyperthermia can contribute to fatigue, probably via effects on th e central nervous system. Appropriate training programs and nutritional interventions enhance fatigue ristance and exercise performance by improving the ability of the muscles to su stain ATP production.