Telomerase expression is silenced in most adult somatic tissues with the exception of adult stem cell (SC) compartments, which have the property of having the longest telomeres within a given tissue. Adult SC compartments suffer from telomere shortening associated with organismal aging until telomeres reach a critically short length, which is sufficient to impair SC mobilization and tissue regeneration. p53 is essential to prevent that adult SC carrying telomere damage contribute to tissue regeneration, indicating a novel role for p53 in SC behavior and therefore in the maintenance of tissue fitness and tumor protection. Reprogramming of adult differentiated cells to a more pluripotent state has been achieved by various means, including somatic cell nuclear transfer and, more recently, by over expression of specific transcription factors to generate the so-called induced pluripotent stem (iPS) cells. Recent work has demonstrated that telomeric chromatin is remodeled and telomeres are elongated by telomerase during nuclear reprogramming. These findings suggest that the structure of telomeric chromatin is dynamic and controlled by epigenetic programs associated with the differentiation potential of cells, which are reversed by reprogramming. This chapter will focus on the current knowledge of the role of telomeres and telomerase in adult SC, as well as during nuclear reprograming to generate pluripotent embryonic-like stem cells from adult differentiated cells.