The molecular mechanisms of somatic cell reprogramming, including the role of endogenous determinants, remain poorly understood. Here we review the role of the homeodomain protein Nanog during induced pluripotency. Nanog is not required to trigger somatic cell reprogramming. Instead, Nanog is specifi cally required to fi nalize reprogramming in chemically defi ned conditions that support naive pluripotency. This closely resembles mouse embryogenesis, where Nanog controls the emergence of the naive pluripotent epiblast from a transcriptional network primed by other factors, including Oct4. Constitutive expression of Nanog enhances reprogramming and enables induced pluripotency in conditions that normally do not support the self-renewal of embryonic stem cells. We discuss the proposed mechanisms leading to the transcriptional activation of Nanog and its mode of action during reprogramming.