Advances in cardiovascular research during the past two decades have resulted in an improved understanding of the chain of events that lead to end-stage coronary artery disease. These developments have been paralleled by therapeutic advances that now make it possible to intervene at virtually every stage in the development of advanced cardiac disease, from asymptomatic persons at risk of developing coronary atherosclerosis to patients with end-stage heart failure. By interrupting this chain of events, perhaps at multiple sites, it may be possible to prevent or slow the development of symptomatic heart disease and hopefully prolong life. Many opportunities exist for obtaining further information regarding the underlying pathophysiology, the fundamental mechanisms of action of interventions designed to prevent and/or treat the development of myocardial ischemia and cardiac failure and for effecting favorably the natural history of various forms of heart disease.