Estrogen receptors are multi-domain proteins that interact with other proteins and DNA to fulfil their function: the regulation of transcription. During the past 2-3 years, our understanding of this complex process has increased tremendously as crystal structures of isolated ligand-binding domains in complex with various ligands, as well as co-activator peptides, are now available. The structural information, combined with new data on novel co-activators/co-repressors, muteins and their actions, and novel ligands, allows for the first time the development of detailed theories for the first steps of transcription initiation.