GHB (γ‐hydroxybutyrate) is not only an endogenously present small molecule but also a clinically prescribed drug for the symptomatic treatment of narcolepsy. However, GHB's mechanism of action remains to be uncovered. Within the CNS, GHB targets both GABAB receptors and a pharmacologically distinct population of high‐affinity binding sites with unknown molecular identity. HOCPCA (3‐hydroxycyclopent‐1‐enecarboxylic acid) is a structural analog of GHB selectively targeting GHB high‐affinity binding sites. Here, we discuss the usefulness of 3H‐ and 11C‐labeled HOCPCA as radioligands for selectively probing GHB high‐affinity binding sites and their application in drug discovery. As such, 3HHOCPCA's exceptional affinity and selectivity makes it an indispensable tool in drug discovery, and its utility has been demonstrated in, for example, homogenate binding studies, in vitro as well as ex vivo autoradiography. Moreover, the successful synthesis of 11CHOCPCA is a starting point for further ligand development for future in vivo investigations of GHB high‐affinity binding sites. The usefulness of radiolabeled HOCPCA for selectively labeling brain‐specific GHB high‐affinity binding sites both in vitro and in vivo is reviewed. 3HHOCPCA proves to be a highly useful tool to study GHB's pharmacology.