Embryonic stem (ES) cells are characterized by their ability to self-renew and remain pluripotent. Transcription factors have critical roles in the maintenance of ES cells through specifying an ES-cell-specific gene expression program. Deciphering the transcriptional regulatory network that describes the specific interactions of these transcription factors with the genomic template is crucial for understanding the design and key components of this network. Recent advances in genomic technologies have facilitated genome-wide disclosure of the repertoire of transcription-factor-binding sites. Transcription factor colocalization hot spots targeted by multiple transcription factors have been identified. These are sites that integrate the external signaling pathways to the transcriptional regulatory circuitry governed by Oct4, Sox2, and Nanog. In addition, these sites may serve as focal points for the assembly of nucleoprotein complexes known as enhanceosomes. Studying the properties of ES-cell-specific enhanceosomes in different pluripotent cells will shed light on the composition and regulation of their activity. Knowledge of the transcriptional regulatory networks in different pluripotent cells will also help to distinguish the core and peripheral parts of the networks. Collectively, these studies will facilitate the understanding of molecular mechanisms behind transcription-factor-mediated regulation of pluripotent stem cells.