Embryonic stem cells (ESCs) are pluripotent cells which have the capability of differentiating into many different cell types. A complex transcriptional network consisting of Oct4, Sox2 and Nanog maintains ESCs in undifferentiated state while being poised to be directed into different committed cell types. Recently, tremendous efforts have made to elucidate the functions of cofactors in ESC identity and differentiation. More and more evidence has shown that cofactors are very crucial for both pluripotency maintenance and differentiation capacity in ESCs. Cofactors do not bind to DNA directly. Rather, they are usually recruited to target sites by transcription factors or epigenetic marks. Transcriptional cofactors including co activators or co repressors serve as critical components of the regulatory circuitry that ensures unique gene expression program in ESCs. This blog highlights the recent findings on the functions of transcriptional cofactors and the underlying molecular mechanism that maintains ESC identity.