The promise of generating truly pluripotent stem cells from terminally differentiated adult cell types continues to captivate scientists who envision great potential for therapeutic interventions. The two primary methods involve either the replacement of oocyte nuclei with adult somatic cell nuclei—a process known as somatic cell nuclear transfer (SCNT)—or the introduction, typically by viruses, of a cocktail of specific transcription factors to create induced pluripotent stem cells (iPSCs). SCNT is more efficient and less variable but technically more demanding, and the availability of high-quality oocytes is limited. Thus, the potential to combine these approaches by identifying the crucial factors in oocytes that mediate SCNT efficiency is reviewed in a new article published in Stem Cells and Development.