Reprogramming shifts somatic cells toward a pluripotent state, resulting in cells that are capable of producing any tissue type, which provides a unique system for regenerative medicine. However, the poor efficiency of this process has prevented the use of induced pluripotent stem cells (iPSCs) in clinical application of stem cell biology. Importantly, more recent work has highlighted novel reprogramming factors and new strategies to enhance the reprogramming process. In this review, we focus on the transition of somatic cells to iPSCs, effective routes to improve the reprogramming efficacy, and the potential mechanism underlying this process.