Metal ions are essential both in biological systems, where they function as nutrients and therapeutic agents, and in the global economy, where they enable advanced technologies. Purposefully designed chelators bridge these domains by enhancing the biological performance of metal ions and by enabling the enrichment, isolation, and separation of technologically critical metals. This presentation highlights our group’s recent efforts in chelator design for these two areas. In the first part, we survey how expanded macrocyclic chelators can be engineered for nuclear medicine. Our studies show that introducing controlled flexibility into these ligands allows them to adjust their binding conformations to accommodate metal ions of varying sizes, increasing their versatility for radiometal-based applications. The second part focuses on applying this chelator class to the extraction and separation of rare earth elements, critical minerals central to modern technologies. We demonstrate how rationally tailored chelators can selectively remove and enrich rare earths from complex matrices and enable efficient interelement separations. Together, these studies illustrate how fundamental principles of coordination chemistry can be leveraged to meet distinct challenges in nuclear medicine and critical mineral processing.