The last few years have witnessed growing interest in regenerative therapy for the failing heart by cell transplantation. Although initial studies with skeletal myoblasts are more than 10 years old, the potential of bone marrow-derived cells has led to a flurry of experimental studies generating generally positive but occasionally contradictory results. This has given rise on not a few occasions to conflicting viewpoints regarding the ethics of initiating clinical trials. We feel it is appropriate to offer a critical view of the use of stem cells for heart failure. Perhaps the thorniest question to answer at this time is whether clinical trials are justified or not in the light of current knowledge, or whether we should acquire deeper knowledge of the possible efficacy and safety of this type of treatment, and of the mechanisms that account for its efficacy, before we so much as initiate studies in humans. We feel there is now sufficient evidence to justify the performance of clinical trials despite the undoubtedly numerous questions that remain to be answered with experimental studies in animals.