Controversies in stem cell therapy for cardiovascular regeneration/repair highlight the need to go back to the root of the problem and analyze the reasons for the current ideological stagnation. Technological advancements are often advocated to overcome a scientific stalemate. However, technology does not suffice without a clear physiological understanding of stem cell biology as a component of the general feedback response to injury. This viewpoint opines that endogenous mechanisms of repair are incompletely understood, and more research is needed in humans and experimental models to dissect the role of stem cells in the pathogenesis of cardiovascular diseases.