Abstract: Circumstantial studies indicated that incomplete or inappropriate epigenetic reprogramming of donor nuclei was likely to be the primary reason for failures in nuclear transfer. In this view, we discussed the roles of several epigenetic mechanisms, including DNA methylation, chromatin remodeling, imprinting and X chromosome inactivation, telomere maintenance, and epigenetic inheritance in the observed abnormalities in clones from different species. Understanding the mechanisms underlying epigenetic reprogramming control will help us resolve the inherent problems in nuclear transfer technology and make its applications promising.