Analyses of recently sequenced sponge, cnidarian, placozoan, and choanoflagellate genomes have revealed that most transcription factor (TF) classes and families expressed during bilaterian development originated at the dawn of the animal kingdom, before the divergence of contemporary animal lineages. The ancestral metazoan genome included members of the bHLH, Mef2, Fox, Sox, T-box, ETS, nuclear receptor, Rel/NF-kappaB, bZIP, and Smad families, and a diversity of homeobox-containing classes, including ANTP, Prd-like, Pax, POU, LIM-HD, Six, and TALE. As many of these TF classes and families appear to be metazoan specific and not present in choanoflagellates, fungi and more distant eukaryotes, their genesis and expansion may have contributed to the evolution of animal multicellularity.