Stem cell therapy for cardiac disease is an exciting but highly controversial 
research area. Strategies such as cell transplantation and reprogramming have 
demonstrated both intriguing and sobering results. Yet as clinical trials 
proceed, our incomplete understanding of stem cell behavior is made evident by 
numerous unresolved matters, such as the mechanisms of cardiomyocyte turnover or 
the optimal therapeutic strategies to achieve clinical efficacy. In this 
Perspective, we consider how cardiac stem cell biology has led us into clinical 
trials, and we suggest that achieving true cardiac regeneration in patients may 
ultimately require resolution of critical controversies in experimental cardiac 
regeneration.