The transcription factors Oct4, Sox2 and Nanog form a triumvirate of regulatory proteins governing efficient maintenance of pluripotent cell identity. However, in contrast to Oct4 and Sox2, whose protein levels are relatively constant in undifferentiated mouse ES cells, Nanog levels fluctuate widely. Here, we discuss the effect of altering the dose of Nanog on self-renewal efficiency. The key role of Nanog as a self-renewal rheostat and the fact that fluctuations in Nanog level allow entry of Nanog-low cells into a differentiation-prone state are presented in relation to interactions of Nanog not only with itself but also with its partner proteins. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.