Nearly ten years after the first cloned mammal was born, nuclear transfer into enucleated oocytes still rarely yields viable mammalian embryos –most cloned embryos implant normally but die after the blastocyst stage. Jouneau and co-workers now report that mouse embryos produced by the transplantation of embryonic stem cell nuclei into enucleated mouse oocytes(ES NT embryos) fail to develop primarily because of trophoblast defects– defects that are characterised by trophoblast overgrowth and subsequent placental abnormalities (see p. 1597). The researchers use embryological studies, gene expression analyses and experiments with chimeric embryos to investigate why ES NT embryogenesis fails. They show, for example, that the peri-implantation death of ES NT embryos can be partly rescued through the injection of normal ES cells or inner cell mass cells. Based on their results, the researchers propose that ES NT embryos fail because of defective epigenetic reprogramming in the trophoblast lineage. Future work should determine whether the same is true for cloned embryos produced by somatic cell nuclear transfer.