In the past few years our understanding of nuclear receptor (NR) action has been dramatically improved. This is due to to advancements in three fields, (i) 3D structure determination, (ii) analysis of the complexes formed between nuclear receptors and co-regulatory molecules, and (iii) the genetic analysis of nuclear receptor signalling by gene "knock out" and "knock in" technologies. The elucidation of the crystal structure of apo-, holo (agonist)- and antagonist-NR ligand-binding domain (LBD) complexes is of outstanding importance for our understanding of the structural principles, in particular of the ligand-induced allosteric alterations, that are at the basis of receptor action. The concomitant identification and functional analysis of co-regulators (TIFs, coactivators and co-repressors) previously predicted from squelching studies have provided the possibility to understand the propagation of the original signal from ligand binding through intramolecular allosteric effects to intermolecular interactions. Recent crystal data of receptor LBD heterodimers and LBD-agonist complexes with nuclear receptor interacting peptides of co-activators have provided molecular insights into receptor dimerization and receptor-coactivator interaction. Finally, analysis of the signalling compexes established over nuclear receptors, assembling enzymatic activities that can alter the acetylation status of chromatin at the promoter regions of target genes and (de)acetylate other transcription regulatory factors paves the way to a comprehension of receptor action at the chromatin level. But much remains to be learnt and the recent studies have pointed towards an enormous complexity of this signalling system. Insights into the mechanistic basis of promyelocytic leukemia and the role of retinoic acid in differentiation therapy have been obtained as a consequence of the above studies, justified the efforts and led to an increasing awareness of the nuclear receptor signalling systems in basic and applied research. Here we will review recent data with the focus on what we have learnt about the interplay between NR structure and function to provide a view of the early steps of nuclear receptor action.