Cell transplantation is gaining interest as a potentially new means of improving function of the failing heart through replacement of lost cardiomyocytes with new contractile cells. Primarily for practical reasons, autologous skeletal myoblasts have been the first to undergo clinical trials but other cell types are also being considered, particularly bone marrow stem cells which are credited for a plasticity that might allow them to change their phenotype in response to environmental cues. Several key issues still need to be addressed including: the comparative efficacy of different donor cell lineages in relation to the patient's clinical condition (i.e., ischemia vs. heart failure, the mechanism by which cell engraftment improves cardiac function, the enhancement of cell survival and functional integration within the recipient tissue, and the development of minimally invasive cell delivery techniques. In parallel to these laboratory studies, clinical trials are now being implemented to generate efficacy data. Altogether, these efforts should allow the assessment of whether and to what extent cell transplantation may ameliorate function of the failing heart. © Future Drugs Ltd. All rights reserved.