Events after fertilisation have been carefully studied in the last decades. However, there are still several questions to be clarified in relation to the signalling pathway initiated by the sperm, the identification of proteins or factors involved in the activation of the arrested oocyte, and the inactivation of specific molecules involved in the meiotic arrest. The present state of knowledge in mammalian fertilisation allows the development of activation protocols that closely mimic the events initiated by the sperm according to certain major factors (MPF activity and MAPk activity). These protocols are successfully used for the activation of oocytes after NT giving rise to offspring. Few cloned animals have yet been produced. However, the pregnancy and the survival rates after birth are not significantly different when different activation protocols are compared. This fact argues fora major reason forthe low success in the efficiency of NT. Eventually, factors related to the recipient oocyte, the donor cell or the culture conditions are part of these major problems that the reconstructed embryo has to overcome to develop into a normal offspring. Nonetheless, the development of activation protocols that closely imitate the mechanism of activation initiated by the sperm are of special interest to improve the developmental potential of cloned embryos.