Nuclear hormone receptors are not only important drug targets, but have also been the focus of decades of active and highly insightful research. Ten years ago, a review on nuclear receptors was entitled The Second Decade and a special issue of Molecular Endocrinology in 2005 dealt with the results of these research efforts. The consensus from nuclear receptor research was of course that the signaling pathways mediated by these receptors warrant further research, even though in principle they appeared to represent the most immediate, seemingly simple signaling pathway from hormone (ligand)...