Embryonic stem (ES) cells derived from the inner cell mass of developing embryos have tremendous potential in regenerative medicine due to their unique properties: ES cells can be maintained for a prolonged time without changes in their cellular characteristics in vitro (self-renewal), while sustaining the capacity to give rise to all cell types of adult organisms (pluripotency). In addition to the development of protocols to manipulate ES cells for therapeutic applications, understanding how such unique properties are maintained has been one of the key questions in stem cell research. During the past decade, advances in high-throughput technologies have enabled us to systematically monitor multiple layers of gene regulatory mechanisms in ES cells. In this review, we briefly summarize recent findings on global gene regulatory modes in ES cells, mainly focusing on the regulatory factors responsible for transcriptional and epigenetic regulations as well as their modular regulatory patterns throughout the genome.