Stem-cell therapy provides the prospect of an exciting and powerful treatment to repair the heart. Although research has been undertaken in animals to analyse the safety and efficacy of this new approach, results have been inconclusive. The mechanism by which stem cells could improve cardiac function remains unclear. We describe the background to the concept of natural repair and the work that has been done to establish the role of stem cells in cardiac repair. Controversies have arisen in interpretation of experimental data. The important issues surrounding the application of stem-cell therapy to man are discussed critically. We discuss the future of this pioneering work in the setting of growing concerns about clinical studies in man without understanding the biological mechanisms involved, with the difficulties in funding this type of research.