Nuclear transfer of a somatic nucleus into an enucleated oocyte has demonstrated in several mammalian species that the chromatin of a differentiated nucleus can be reprogrammed so as to be able to direct the full development of the reconstructed embryo. This review focus on the timing of the early events that allow the return of somatic chromatin to a totipotent state. Our understanding of the modifications associated with chromatin remodeling is limited by the low amount of biological material available in mammals at early developmental stages and the fact that very few genetic studies have been conducted with nuclear transfer embryos. However, the importance of several factors such as the covalent modifications of DNA through the methylation of CpG dinucleotides, the exchange of histones through a reorganized nuclear membrane, and the interaction between cytoplasmic oocyte components and nuclear complexes in the context of nuclear transfer is becoming clear. A better characterization of the changes in somatic chromatin after nuclear transfer and the identification of oocyte factors or structures that govern the formation of a functional nucleus will help us to understand the relationship between chromatin structure and cellular totipotency.