The regulation of eukaryotic genes almost always depends on cooperative interactions between factors. This is essential to allow the rich array of transcriptional responses required for both development and adaptation to the environment. We are only beginning to decipher the mechanisms governing this cooperativity, which include processes such as the cooperative assembly of large DNA-bound protein complexes and the cooperative recruitment of positively and negatively acting co-regulatory proteins.One of the hopes of the genomics revolution is that we will eventually be able to predict how a gene will function, for example, in development, by simply analyzing its sequence. Given the conservation in protein coding sequences between diverse organisms, it is highly likely that the evolution of developmental complexity is due more to the evolution of enhancers than to the evolution of coding regions. If we are ever to predict developmental phenotypes from gene sequences, it will be essential to gain a better understanding of the mechanisms by which transcription factors cooperate with one another to define transcriptional states.Suggestions for further reading