Somatic cell reprogramming consists of the induction of a complex sequence of events that results in the modification of the developmental state of the cell. It is now routinely possible to reprogram fully differentiated cells back to pluripotent cells, and to transdifferentiate cells of a given type in cells of a totally different lineage origin. However, whether there are key initiating factors that are distinct from those that control stem-cell renewal and that can initiate the reprogramming process remains unknown. In contrast, what is clear is that, by modifying the epigenetic status of a cell, its reprogramming can be initiated. Here, we review the current literature that shows how the plasticity of a cell can be modulated by modifying its epigenetic status, and we discuss how epigenetic barriers can be removed, to induce an efficient reprogramming process.