Characterization and cloning of liver-enriched transcription factors have provided the tools to study the regulation of liver differentiation. Characterization of the temporal and spatial expression of these factors have shown a sequential order of appearance, in coordination with the expression of their target genes, during liver development. Evidence has accumulated showing cooperation between distinct factors in regulating liver-specific gene expression. Since each of these factors is not uniquely expressed in the liver, yet, the liver is the only tissue that expresses all of these factors, the cooperation between the coexisting liver-enriched factors could constitute the basis for the regulation of liver-specific gene expression.