Adult skeletal muscle provides a unique paradigm for studying stem to differentiated cell transitions. In response to environmental stress, quiescent muscle stem cells (satellite cells) are activated and proliferative, at which stage they can either differentiate and fuse to form new muscle fibers or alternatively self-renew and maintain the muscle stem cell reservoir. This multi-step myogenic process is orchestrated by muscle regulatory proteins such as Pax3/Pax7 and members of the MyoD family of transcription factors. Findings published over the past few years have uncovered that epigenetic mechanisms critically repress, maintain or induce muscle-specific transcriptional programs during myogenesis. These studies are increasing our understanding of how muscle lineage-specific information encoded in chromatin merges with muscle regulatory factors to drive muscle stem cells through transitions during myogenesis.