Pluripotent stem cells have long-term proliferative capacity and an unusual mode of cell-cycle regulation and can divide independently of extrinsic mitogenic signals. The last few years has seen evidence emerge that links cell-cycle regulation to the maintenance and establishment of pluripotency. Myc transcription factors appear to be central to this regulation. This review addresses these links and discusses how cell-cycle controls and Myc impact on the maintenance and establishment of pluripotency.