The importance of the adopted metabolite receptors, such as PPAR, LXR, and FXR, in transcriptional control of metabolic pathways has been appreciated for many years. However, it is becoming increasingly clear that the number of nuclear receptors with roles in metabolism is much larger than initially suspected. Recent years have brought an intense effort to define the biological functions of the most enigmatic group of the nuclear receptor superfamily, the true orphan receptors, including NR4As, ERRs, RORs, and Rev-erbs. Unexpectedly, several of these receptors also turn out to have important functions in various aspects of metabolic control.