The recent discovery that it is possible to directly reprogramme somatic cells to an embryonic stem (ES) cell-like pluripotent state, by retroviral transduction of just four genes (Oct3/4, Sox2, c-Myc and Kif4), represents a major breakthrough in stem cell research. The reprogrammed cells, known as induced pluripotent stem (iPS) cells, possess many of the properties of ES cells, and represent one of the most promising sources of patient-specific cells for use in regenerative medicine. While the ultimate goal is the use of iPS cells in the treatment of human disease, much of the research to date has been carried out with murine cells, and improved mouse iPS cells have been shown to contribute to live chimeric mice that are germ-line competent. Very recently, it has been reported that iPS cells can be generated by three factors without c-Myc, and these cells give rise to chimeric mice with a reduced risk of tumour development.