In high-income countries, coronary artery disease is one of the most frequent cardiovascular disorders, and leads to acute myocardial infarction. Myocardial infarction frequently progresses into maladaptive cardiac remodeling and heart failure. Ultimately, transplantation remains the only therapeutic option. However, the lack of organ donors limits the access to transplantation to a small number of patients each year. In this context, induction of cardiac regeneration in the damaged heart could represent an attractive therapeutic approach. This will only be possible if the pathways important for inducing repair and their associated regulatory mechanisms are identified. In the damaged heart, compensatory myocyte hypertrophy maintains cardiac output. Recent evidence suggests, however, that myocytes could be replaced continuously through a process involving replication, differentiation, senescence and death. Along these lines, resident cardiac stem cells have been identified. Together, this indicates that, akin of prototypic self-renewing tissues, the heart could possess the basic and necessary elements for tissue regeneration.