In this chapter we first summarise the current knowledge about the phylogenetic spectrum of nuclear receptors (NRs). Then, we discuss how studying their diversity can be helpful to make insights about their evolution. Significant attention is paid to the evolution of ligand-binding ability. Recent evolutionary and functional data have challenged the traditional concept of ligand, providing a more complex view of the mechanisms by which the transcriptional activity of NRs can be modulated. Finally, we argue that the evolutionary analysis of NRs has contributed to a conceptual shift of our understanding of nuclear receptors, from highly specific endocrine regulators to a promiscuous metabolic rheostat.