Embryonic stem (ES) cells have the capacity to form every type of cell in our adult bodies due to their pluripotency. The prospective use of ES cells in regenerative therapies for human diseases such as Parkinson’s disease and diabetes has raised the interest in identifying the mechanisms that allow these cells to maintain pluripotent fate and differentiate along many lineages. However, ethical questions regarding the use of human eggs andor embryos for medical research have limited the ability of scientists to develop therapies with human ES cells. Three recent papers in Nature and Cell Stem Cell have revealed novel methods of reprogramming somatic cells into cells with the same pluripotent potential as ES cells via the expression of only four transcription factors. These scientific advances illuminate the mechanisms that drive pluripotent fate in embryonic cells. In addition, by giving scientists a model to study ES-like cells that are not derived from embryos, these newly identified models have the potential to progress therapies for regenerative medicine.