During the past decades, different variants of the Fontan circulation have become the primary therapeutic option for physiological correction of congenital cardiac malformations in which restoration to biventricular circulations is impossible. Subsequent to creation of the Fontan circulation, the pulmonary and systemic circulations are in series, with only one pumping chamber. Thus, the functionally single ventricle must provide energy for flow of blood to the lungs, as well as to the body. Generally, patients who have undergone these procedures have a good prognosis, although they have subnormal cardiac output at rest, while their central venous pressure is significantly elevated. Despite an adequate haemodynamic situation at rest, exercise performance is usually reduced. Thus far, this reduction has been attributed to cardiac factors, such as the absence of the morphologically right ventricle, or impaired function of the morphologically left ventricle. Due to the mechanical coupling between the heart and the peripheral circulation, however, the inadequate response to exercise in terms of cardiac output might also be dependant on insufficient peripheral vascular adjustments. In this review, we assess the existing experimental and clinical studies which provide detailed analysis of ventriculo-arterial mechanics in the setting of the Fontan circulation.