Nuclear receptors are transcription factors that often respond to small molecule metabolites and fat-soluble compounds to regulate gene expression. They broadly govern development, reproduction, metabolism, and homeostasis in diverse metazoan species and their dysregulation is associated with numerous diseases. Work in C. elegans has shed light on the seminal role of nuclear receptors in life history regulation, stem cell progression, developmental timing, cell fate specification, nutrient sensing, metabolism, and longevity. Here we highlight recent advances on the best-studied nuclear receptors in the worm, and how they illuminate metazoan biology.