The aim of the current literature study was to perform a literature review of the factors contributing to exercise limitation and physiological response to exercise in patients with Fontan circulation. In patients with Fontan circulation, peak oxygen uptake ranged from about 14.4 to 32.3 ml/min/kg, and showed a slowed acceleration in the kinetics of oxygen uptake at the onset of exercise. Peak heart rate during exercise was decreased to an average of 153 +/- 10 bpm and arterial oxygen saturation was also decreased at peak exercise, with an average of 89.5 +/- 1.94%. Cardiac output was subnormal, owing to reduced stroke volume, heart rate response and affected pulmonary venous return. Ventilatory anaerobic threshold was below normal values. Moreover, the ventilatory equivalent for carbon dioxide was found to be higher. Patients with Fontan circulation possess a unique physiological response to exercise. Although there is a wide range in exercise capacity among patients, all patients have reduced tolerance to exercise. Cardiac, pulmonary, and muscular factors might play a role in reduced exercise capacity and this distinct response to exercise.