The heart is a simple organ burdened with the pivotal task of maintaining circulation. Yet, despite its importance to life, the adult mammalian heart has little regenerative capacity. Not surprisingly, this deŒciency plays amajor role in making cardiovascular disease the leading cause of death in the United States as well as in the Western world. In fact, myocardial infarction ranks as the leading cause of death as well as the most costly medical condition to treat, killing over 750,000 Americans each year (Lloyd-Jones et al. 2010; Roger et al. 2012). Furthermore, common invasive procedures such as bypass surgery or angioplasty are temporary remedies, as the reoccurrence of asecond myocardial infarction is approximately 14% within ayear of the Œrst incident (Holmes et al. 2005; Reeve et al. 2005; Bolli and Chaudhry 2010). In response to myocardial infarction, dead, necrotic heart tissue is replaced by dense, collagen-laden scar tissue (Holmes et al. 2005). While scarring is an essential cellular response to preserve remaining heart function, over time, this non-contractile, rigid Œbrotic tissue causes arrhythmia. In contrast, teleosts, like the zebraŒsh, have aremarkable capacity to regenerate damaged cardiac tissues throughout their lifetime, thus making it an ideal model system to elucidate the cellular and genetic basis for cardiac tissue regeneration.