Cardiovascular progenitor cells (CPCs) are a promising cell source for cardiac regenerative therapy owing to their ability for self-renewal and differentiation into various cardiovascular cell types beneficial for myocardial repair: cardiomyocytes, smooth muscle cells, and endothelial cells. Previous evaluations of exogenously derived CPCs have focused mainly on their capacity for tri-lineage differentiation rather than self-renewal, owing to the lack of an effective protocol to maintain and expand CPCs long-term in culture. In a recent issue of Cell Stem Cell, two groups of investigators independently reported their success in isolating, maintaining, and expanding mouse CPCs in culture for greater than 18 to 20 passages (1010- to 1015-fold expansion), with faithful preservation of progenitor phenotype and ability for tri-lineage-restricted differentiation in both cell culture and mouse models of myocardial infarction. This Commentary will discuss the unique findings of these two studies, highlight the strengths and weaknesses of each CPC derivation/expansion technique, and propose additional steps necessary to accelerate their clinical translation.