Recent studies have shown that orphan GPCRs of the GPR family are utilized as specialized chemosensors in various tissues to detect metabolites, and in turn to activate downstream pathways which regulate systemic homeostasis. These studies often find that such metabolites are generated by well‐known metabolic pathways, implying that known metabolites and chemicals may perform novel functions. In this review, we summarize recent findings highlighting the role of deorphanized GPRs in renal development and function. Understanding the role of these receptors is critical in gaining insights into mechanisms that regulate renal function both in health and in disease. This article is protected by copyright. All rights reserved.