The defining characteristic of a pluripotent stem cell is that is has the potential to self renew and the capacity for differentiation into derivatives of the three embryonic germ layers; endoderm, mesoderm and ectoderm, from which all somatic tissues in an organism can be traced. This full potentiality makes them particularly suitable for developing cell replacement therapies or establishing cellular model systems. Although ES cells may be ideal in terms of their pluripotency, from a therapeutic point of view, their great disadvantage is that they are not patient derived. More recently, advances in medical biology have shown that the genomic state of a somatic cell can be altered or ‘reprogrammed’ to become pluripotent. This is a significant leap forward for obtaining patient-specific pluripotent stem cells that can then be differentiated to the cell type of interest. Generation of reprogrammed somatic cells, known as induced pluripotent stem (iPS) cells, was initially performed by ectopic expression of four transcription factors, however, now this process is becoming more streamlined by improved methods. Through these advances, critical factors and mechanisms involved in driving pluripotency are being determined. This chapter provides a review on how pluripotency is defined and examined in vitro and in vivo. The various ways in which pluripotent stem cells are generated, particularly in relation to induced pluripotency, are also discussed. Finally an outline of disease-specific pluripotent stem cells is reviewed within the context of their capacity to generate the cell type of interest.