Pluripotent stem cells are capable of differentiation into different cell types, and therefore have great potential in clinical applications. The achievement of transcription-factor-induced pluripotent stem cells ( iPS cell) avoids ethical issues and offers an invaluable source of patient-specific pluripotent stem cells for disease modeling, drug screening, toxicology tests, personalized medicine selection, cell therapy and regenerative medicine. As a milestone, iPS technology initiates a new era of pluripotent stem cells. However, even untill now many problems especially the key molecular mechanism of epigenetic reprogramming during this process, are little understood. Uncovering the molecular mechanism of this unique platform would shed light on improving the reprogramming efficiency and iPSC quality, ultimately advancing their therapeutic applications. In this paper we will briefly introduce the significant progress in this field and attach importance to combining high-throughput sequencing technique and systematic biology in future research.