Nuclear receptors (NRs) are molecular transducers of endocrine and dietary signals allowing tissues to adapt their transcriptional responses to endogenous or exogenous cues. These signals act in many cases as specific ligands, converting of NRs into transcriptionally active molecules. This on-off mechanism needs, however, to be finely tuned with respect to the tissue environment and adjusted to the organism needs. These subtle adjustments of NR transcriptional activity are brought about by post-translational modifications (PTMs), which can be, in the case of orphan NRs, the sole regulatory mechanism. The role of PTMs, with a more specific focus on phosphorylation, affecting the functions of NR controlling metabolic events is described in this review.