Somatic cell nuclear transfer (SCNT) is a technically and biologically challenging procedure during which a differentiated committed nucleus undergoes rapid reprogramming into the totipotent state in a few hours. SCNT can be utilized to generate patient- and disease-specific embryonic stem cell (ESC) lines, which carry great promise in improving our understanding of major disease conditions and hope for better therapies. In this section, we will describe how mouse SCNT is performed and survey the importance of donor cell cycle synchronization and the methods to perform it.