The remarkable capacity of the liver to regenerate after severe injury or disease has excited interest for centuries. The goal of harnessing this process in treatment of liver disease, and the appreciation of the parallels between regeneration and tumor development in the liver, remain a major driver for research in this area. Studies of liver regeneration as a model system offer a view of intricate and precisely timed regulatory pathways that drive the process toward completion. Successful regeneration of the liver mass demands a hierarchal and well-controlled balance between proliferative and metabolic functions, which is orchestrated by signaling and regulation of transcription factors. Control and regulation of these cascades of transcriptional activities, necessary for induction, renewal, and cessation of liver growth, are the focus of this chapter.