The groundbreaking discovery, that somatic mammalian cells can be epigenetically reprogrammed to a pluripotent state through the exogenous expression of the transcription factors Oct4, Sox2, Klf4 and c-myc, has yielded a new cell type for potential application in regenerative medicine, the induced Pluripotent Stem Cells (iPSCs). Since the first demonstration of creating iPSCs in 2006 great efforts have been made into improving iPS cell generation methods and understanding the reprogramming mechanism as well as the nature of iPSCs. The iPSCs technique makes it possible to produce patient-specific pluripotent stem cells for transplantation therapy without immune rejection. However, some restriction still remain, including viral vector integration into the genome, the existence of exogenous oncogenic factors and low induction efficiency. In this review we discuss recent advances in methods of generating safer iPSCs lines and their possible use for biomedical applications.