The article by Laflamme and Murry reviews the current state of heart regeneration research, focusing on the challenges and progress in understanding and therapeutic approaches. Heart failure, a leading cause of death in industrialized nations, is often due to a deficiency of cardiomyocytes. While lower vertebrates like zebrafish exhibit robust heart regeneration, mammalian hearts have limited regenerative capacity. The authors discuss the evidence for cardiomyocyte turnover in humans, which is slow and difficult to detect. They review experimental strategies using adult and pluripotent stem cells, cellular reprogramming, and tissue engineering to enhance heart repair. Despite significant advancements, challenges remain, including the need for better tools to study cardiomyocyte proliferation and the development of more efficient protocols for generating cardiomyocytes. The article highlights the potential of stem cell therapies and tissue engineering to improve heart function after injury, but emphasizes the need for further research to overcome current limitations.The article by Laflamme and Murry reviews the current state of heart regeneration research, focusing on the challenges and progress in understanding and therapeutic approaches. Heart failure, a leading cause of death in industrialized nations, is often due to a deficiency of cardiomyocytes. While lower vertebrates like zebrafish exhibit robust heart regeneration, mammalian hearts have limited regenerative capacity. The authors discuss the evidence for cardiomyocyte turnover in humans, which is slow and difficult to detect. They review experimental strategies using adult and pluripotent stem cells, cellular reprogramming, and tissue engineering to enhance heart repair. Despite significant advancements, challenges remain, including the need for better tools to study cardiomyocyte proliferation and the development of more efficient protocols for generating cardiomyocytes. The article highlights the potential of stem cell therapies and tissue engineering to improve heart function after injury, but emphasizes the need for further research to overcome current limitations.