X chromosome inactivation (XCI) is a very good model of epigenetic changes that occur during early development. This essential process occurring in females leads to X-linked gene dosage compensation between the sexes. Recent data suggest that different mammalian species may use different strategies to initiate XCI during early embryogenesis. In mice, XCI occurs in two waves, imprinted during preimplantation then random in the embryo. In humans, XCI is not imprinted and has not yet been triggered at the blastocyst stage. These results highlight the remarkable diversity of XCI mechanisms.