Cardiovascular diseases are the leading causes of death in the western world. The fact that cardiovascular mortality and morbidity rates increase exponentially in the elderly suggests that age per se is a major risk factor for cardiovascular diseases. Data from the Framingham Heart study and the Baltimore Longitudinal Study on Aging showed an age-dependent increase in left ventricular hypertrophy, diastolic dysfunction, atrial fibrillation, and decline in exercise capacity. Experimental evidence shows that cardiac aging in the mouse closely recapitulates that found in humans. The evolutionary conservation of intrinsic cardiac aging is demonstrated by studies in Drosophila melanogaster, and this model offers unique genetic insights into cardiac aging. In this chapter we summarize the biology of cardiac aging in humans, rodents, flies, dogs and primates. Murine and Drosophila models of cardiac aging have been valuable to elucidate the molecular mechanisms of cardiac aging and increase vulnerability in the aged heart. This chapter highlights the mechanistic role of mitochondrial oxidative stress, insulin-IGF1, the renin-angiotensin system and adrenergic signaling, as well as the aging of cardiac stem cells. The mechanism of progression to heart failure in aged hearts and the effect of dietary restriction are also discussed. As the number of elderly persons is predicted to double in the next 25 years and the prevalence of age-related cardiovascular disabilities continues to increase, there is an urgent need to understand the biology of the aging heart, the mechanisms for age-mediated cardiac vulnerability and to use these insights to develop strategies to ameliorate myocardial dysfunction in the elderly.