MYC and MYCN have been directly implicated in the transcriptional regulation of several thousand genes in pluripotent stem cells and possibly contribute to the activity of all transcribed genes. Control of transcription by a pause-release mechanism, recruitment of positive and negative epigenetic regulators, and a general role in transcriptional amplification have all been implicated as part of the broad, overarching mechanism by which MYC controls stem cell biology. As would be anticipated from the regulation of so many genes, MYC is involved in a wide range of cellular processes including cell-cycle control, metabolism, signal transduction, self-renewal, maintenance of pluripotency, and control of cell fate decisions. MYC transcription factors also have clear roles in cell reprogramming and establishment of the pluripotent state. The mechanism by which MYC accomplishes this is now being explored and promises to uncover unexpected facets of general MYC regulation that are likely to be applicable to cancer biology. In this work we review our current understanding of how MYC contributes to the maintenance and establishment of pluripotent cells and how it contributes to early embryonic development.