Over the past 5 years there has been great excitement and controversy in the scientific, financial, and lay literature for the potential of stem cell-based strategies for the prev- tion and treatment of chronic heart failure (CHF). Not that long ago we believed we were born with a set number of cardiac myocytes and that once damaged there was no hope to replace them. The interest in the field stems from the magnitude of cardiovascular disease in the world. Our ability to treat and help patients survive acute myocardial infarction (MI) has resulted in a near epidemic of CHF. There are more than 5 million Americans who currently carry the diagnosis of CHF. With more than 1 million MIs a year in the United States, there are approx 500,000 new cases of CHF diagnosed each year. The goal of Stem Cells and Myocardial Regeneration is to present, in a coherent manner, the current state of knowledge of stem cell-based therapies for cardiac dysfunction, including current findings in both the laboratory and the clinic trials. The first section of this Stem Cells and Myocardial Regeneration focuses on the magnitude of the problem and the successes and failures of what we consider optimal medical therapy. It is on this background that stem cell-based therapy needs to build.