In brief:The marathon is one of the greatest tests of human endurance. This review article describes the physiological demands and responses of the respiratory, cardiovascular, and muscular systems to marathon running, focusing on the chain of oxygen transport needed to fulfill the aerobic requirements of marathon running. During the race, runners use about 75% of VO2max. Increased levels of ventilation (>80 liters·min−1) have been observed during the marathon. This can lead to decrements in forced vital capacity and respiratory muscle fatigue. Prolonged muscle activity during the run can cause muscle injury such as inflammation and necrosis of muscle fibers. Techniques for augmenting performance include endurance and interval training, diet manipulation, and racing strategy.