The reprogramming of somatic cells to a pluripotent state by the expression of a defined set of exogenous transcription factors represents a significant breakthrough for the use of stem cells in regenerative medicine. It has the potential to make autologous stem cell therapy practical and promote better understanding of the disease processes by generating patient specific stem cells. Several strategies have been used to generate induced pluripotent stem cells (iPSCs) that include nucleic acid and non-nucleic acid-based approaches, with and without epigenetic modifications. The purpose of these different approaches for generating iPSCs, besides understanding the underlying mechanism, is to develop a facile method for reprogramming without genetic alteration, suitable for clinical use. Here, we discuss different strategies for generating iPSCs, with an emphasis on a recent non-cell autonomous approach to reprogram somatic progenitors that regenerate cornea to a pluripotent state through the recruitment of endogenous transcription factors.