Complete recovery of ischemic cardiac muscle after myocardial infarction is still an unresolved concern. In recent years, intensive research efforts have focused on mimicking the physical and biological properties of myocardium for cardiac repair. Here we show how heart regeneration approaches have evolved from cell therapy to refined tissue engineering. Despite progressive improvements, the best cell type and delivery strategy are not well established. Our group has identified a new population of cardiac adipose tissue-derived progenitor cells with inherent cardiac and angiogenic potential that is a promising candidate for cell therapy to restore ischemic myocardium. We also describe results from three strategies for cell delivery into a murine model of myocardial infarction: intramyocardial injection, implantation of a fibrin patch loaded with cells, and an engineered bioimplant (a combination of chemically designed scaffold, peptide hydrogel, and cells); dual-labeling noninvasive bioluminescence imaging enables in vivo monitoring of cardiac-specific markers and cell survival. © 2012 New York Academy of Sciences.