The Fontan operation can create a stable circulation from childhood through early adulthood. However, the absence of a sub-pulmonary pumping chamber leads to a physiology in which exercise capacity is limited and decreases with age starting in adolescence. The limitation in exercise capacity is more pronounced at peak levels of exercise, but is still present during more modest levels of activity. The underlying causes of exercise impairment relate to both central cardiovascular factors (oxygen delivery) and peripheral factors (oxygen extraction). Interventions to improve cardiac preload and to improve lean muscle mass may help to improve exercise capacity and, perhaps, will alter the “natural history” of the progressive decline.