Embryonic stem (ES) cells, derived from the inner cell mass of mammalian blastocysts, have the ability to grow indefinitely while maintaining pluripotency. These properties have raised the hope that ES cells might be used to treat a host of degenerative diseases, such as Parkinson’s disease, spinal cord injury, and diabetes. However, clinical application of human ES cells faces difficulties regarding use of human embryos, as well as tissue rejection following implantation. One way to circumvent these issues is to generate pluripotent cells directly from somatic cells. A critical step toward this goal is the identification of factors that induce pluripotency in somatic cells.