The discovery of induced pluripotent stem (iPS) cells, which are derived from differentiated cells by simply overexpression a few transcription factors, by Shinya Yamanaka in 2006 marks a major landmark in the fields of stem cell biology and regenerative medicine. To unfold the full potential of reprogramming for disease studies and regenerative medicine, we believe that it is important to understand the molecular mechanisms underlying transcription factor‐ induced reprogramming and to carefully characterize the iPS cell state. To this end, during the third year of funding, we have devised a novel screen to identify factors important for the reprogramming process and allow replacement of the original reprogramming factors. We also studied the role of candidate transcriptional and chromatin regulators in the reprogramming process, which led us to identify novel barriers of the reprogramming process and to a better understanding of how chromatin interferes with the reprogramming process. We have also made progress in understanding the function of the reprogramming factors. Regarding human iPS cell lines, we have derived iPS cells from patients carrying X-linked diseases, and are beginning to characterize them molecularly. Together, we hope that our work will contribute to a better understanding of the reprogramming process.