Mammalian development is a highly complex and tightly regulated process. Transcription factors and chromatin remodelers, acting downstream of cell signalling pathways, are the key intrinsic factors which control gene expression. Recent advances in transcriptomics are allowing biologists to begin to unravel the complex biological roles played by these factors. This review focuses on how genome-wide gene expression and chromatin immunoprecipitation studies are expanding our understanding of the roles played by transcription factors and chromatin remodelers during cell fate decisions in development and differentiation.