Animals can be cloned by transferring a somatic cell nucleus into an enucleated oocyte, but the reprogramming of such nuclei to totipotency to create clones seems to depend on the cell-cycle and differentiation state of both the donor and recipient cell. Now, on p. 1953, Dieter Egli and Kevin Eggan reveal that somatic nuclear reprogramming is not cell cycle dependent but does require nuclear transcriptional factors from the recipient cell. The researchers investigated reprogramming efficiency by examining the development of embryos that were produced by combining donor nuclei and recipient cells at various cell cycle and developmental stages. Many stages of the cell cycle are compatible with nuclear reprogramming, they report, provided sufficient host nuclear factors (including the transcriptional regulator Brg1) are retained in the enucleated recipient cell. Furthermore, cell cycle synchrony between the donor and the recipient is not strictly required at the time of nuclear transfer for successful reprogramming. These results, which reveal that reprogramming is remarkably flexible, might help to improve the efficiency of somatic cell nuclear reprogramming.