Cardiac failure is characterised by the loss of cardiomyocytes, and several strategies to replace the lost cell mass are being developed. Animal models have demonstrated the therapeutic potential of several cell types, and both autologous skeletal myoblasts and bone marrow progenitor cells have been tested in preliminary clinical trials. However functional improvements have been modest and the mechanism of benefit is unclear, although myocardial regeneration is not a significant factor. Alternative strategies using autologous resident cardiac progenitor cells or embryonic stem cell-derived cardiomyocytes could recreate de novo myocardium with higher efficiency, although various hurdles must be overcome before these strategies are translated to the clinic.