Recent developments in the field of reprogramming somatic cells to induced pluripotent stem cells (iPSC) has brought the field closer to the exciting possibility of their future clinical application. A number of challenges remain to be addressed before clinical application of reprogrammed stem cells becomes a reality. The main issues are the threat of cancer, control of differentiation to tissue specific stem cells or body organs and the immune response of iPSC-derived cells. The future use of iPSC will require that they are cancer free, do not proliferate and can be contained to the specific injection site for tissue regeneration. This review discusses the recent advances that address these main challenges in the field of cellular reprogramming