Heart disease remains the most frequent cause of death in the general population and is intimately related to aging. Either extreme premature aging or marked longevity may be monogenic, but in most humans aging is a complex polygenic phenomenon. Hypercholesterolemia and hypertension are important factors. Cardiac amyloidosis and vascular elastin degradation may be separate factors. Humans with the greatest longevity are relatively refractory to atherosclerosis. Frequencies of heart deaths among relatives of a heart-death proband without dyslipoproteinemia conform to expectations of a polygenic trait. Careful, attentive medical management of major environmental factors and of heart senescence can result in more successful aging.