Human embryonic stem cells (hESC) appear to be candidates for use in cell-based heart repair because they can be driven in vitro towards a cardiomyogenic lineage. These cells are able to engraft into infarct areas, differentiate into cardiomyocytes and subsequently improve heart function, although it remains uncertain whether these effects are due to the direct force-generating of ESC-derived differentiated cardiomyocytes or to their paracrine effects harnessing endogenous repair mechanisms. From a clinical perspective, the key issue is safety because of the risk that the final cell yield after transplantation may remain contaminated by residual, still pluripotent cells that could cause tumors. Optimization of purification therefore remains a major technical objective. Besides this hESC-specific manufacturing-related issue, hESC also share with all other cells aimed at cardiac repair problems of delivery, sustained survival and immune responses, which need to be addressed if their therapeutic potential is to be fully exploited. © 2014 Woodhead Publishing Limited All rights reserved.