Piperazic acid (Piz) is an intriguing hydrazine-containing amino acid found in a diverse variety of natural products, the majority of which are bioactive. Recently, several approaches have been reported for targeted isolation of Piz-containing molecules, combining spectroscopic techniques for screening Piz moieties with recent advances in Piz biosynthesis. Here, we highlight bioactive natural products recently isolated using these methods and bring into focus structural elucidation challenges impeding the discovery of more Piz-containing molecules.