Heart disease remains the number one cause of death in developed countries. Loss of cardiomyocytes (CMs) due to aging or pathophysiological conditions (for example, myocardial infarction) is generally considered irreversible, and can lead to lethal conditions from cardiac arrhythmias to heart failure. Human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells (iPSCs), can self-renew while maintaining their pluripotency to differentiate into all cell types, including CMs. As such, PSCs represent an unprecedented unlimited ex vivo cell source. In the present thematic series, we have solicited seven review articles to discuss the current state-of-the-art PSC-based approaches for such applications as disease modeling, discovery of novel drugs and therapeutics, cardiotoxicity screening and cell-based myocardial repair, as well as the associated hurdles and potential solutions.