Ischemic heart disease (IHD) is a significant burden to healthcare systems in the world despite substantial advances in risk modification, pharmacological therapy and revascularization therapy. Stem cell therapy is emerging as a novel therapeutic paradigm for myocardial repair. Several cell types including embryonic stem cells, adult stem cells and induced pluripotent stem (iPS) cells have been used for the treatment of ischemic heart disease. But all these engrafted cells must be systematically or locally administered after being expanded in vitro, the rare differentiation into cardiomyocytes and low cellular survival of engrafted cells also limited the efficacy of stem cell therapy. Recent research indicated that it was feasible to reprogramme one mature cell type into another cell type directly by introducing several transcription factors, which was called transdifferentiation. We speculate that cell reprogramming might provide potential new cell sources for therapeutic cardiac regeneration. For these reasons, we hypothesize that converting cardiac fibroblasts to cardiomyocytes and endothelial progenitor cells (EPCs) either in vivo or in vitro might be a possible way for future therapeutic cardiac regeneration. Furthermore we also analyzed the possible difficulties we might face on way to realize this hypothesis.