Today, cell replacement therapy using pluripotent stem cell-derived cardiomyocytes (PSC-CMs) remains a research endeavor, with several hurdles that must be overcome before delivery of PSC-CMs can become a therapeutic reality. In this review, we highlight major findings to date from pre-clinical studies involving delivery of PSC-CMs and consider remaining challenges that must be addressed for successful clinical translation. Our goal is to provide an overview of the current status of cardiomyocyte replacement therapy and what challenges must be addressed before successful clinical translation of such therapies will be possible. Copyright © 2020. Published by Elsevier Inc.