A daily routine of physical activity is highly beneficial in the prevention and treatment of many prevalent chronic diseases, especially of the cardiovascular (CV) system. However, chronic, excessive sustained endurance exercise may cause adverse structural remodeling of the heart and large arteries. An evolving body of data indicates that chronically training for and participating in extreme endurance competitions such as marathons, ultra-marathons, Iron-man distance triathlons, very long distance bicycle racing, etc., can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which generally return to normal within seven to ten days. In veteran extreme endurance athletes, this recurrent myocardial injury and repair may eventually result in patchy myocardial fibrosis, particularly in the atria, interventricular septum and right ventricle, potentially creating a substrate for atrial and ventricular arrhythmias. Furthermore, chronic, excessive, sustained, high-intensity endurance exercise may be associated with diastolic dysfunction, large-artery wall stiffening and coronary artery calcification. Not all veteran extreme endurance athletes develop pathological remodeling, and indeed lifelong exercisers generally have low mortality rates and excellent functional capacity. The aim of this review is to discuss the emerging understanding of the cardiac pathophysiology of extreme endurance exercise, and make suggestions about healthier fitness patterns for promoting optimal CV health and longevity.