Fusion of transplanted stem cells with recipient cardiomyocytes has been observed in murine [13, 60] and porcine model systems [49] . But since these first observations, few have sought to unravel the mechanisms that govern stem cell fusion or to study the implications of cell fusion for stem cell programming. Lack of study reflects the overwhelming opinion that cell fusion occurs too infrequently to be of relevance for stem cell programming and, by corollary, for tissue repair. However, this opinion fails to appreciate the possibility that (1) detection methodologies may be insufficient to accurately gauge the contribution of cell fusion following stem cell transplantation and/or (2) that we might be able to control or increase the frequency of cell fusion to more effectively induce programming of stem cells following transplantation. We have begun to explore this second possibility by co-opting the well-described fusion machinery of viruses. We find that mesenchymal stem cells modified to express viral fusogen VSV-G are more apt to fuse with cardiomyocytes in a pH-dependent manner. vMSC-CM fusion products formed in this way are prone to adopt cardiomyocyte phenotype and morphology. In addition, vMSCs delivered to the myocardium of mice following infarction can fuse with resident cardiac cell types at rates much higher than previous reports of spontaneous fusion [13, 61] and are more apt to fuse at the site of infarction than in the healthy myocardium.