Generating pluripotent stem cells directly from cells obtained from patients is one of the ultimate goals in regenerative medicine. Two "reprogramming" strategies for the generation of pluripotent stem cells from somatic cells have been studied extensively: nuclear transfer to oocytes and fusion with ES cells. The recent demonstration that, in mouse, nuclear transfer into zygotes can also be effective if the recipient cells are arrested in mitosis provides an exciting new avenue for this type of approach. Patient-specific pluripotent cells could potentially also be generated by the spontaneous reprogramming of bone marrow cells, spermatogonial cells, and parthenogenetic embryos. A third overall type of strategy arose from the demonstration that pluripotent stem (iPS) cells can be generated from mouse fibroblasts by the introduction of four transcription factors (Oct-3/4, Sox2, c-Myc, and KLF4). Recent work has underlined the potential of this strategy by improving the efficiency of the process and demonstrating that iPS cells can contribute to many different tissues in vivo, including the germline. Taken together, these studies underscore the crucial roles of transcription factors and chromatin remodeling in nuclear reprogramming.