NMR spectroscopy and X-ray crystallography in conjunction with extended X-ray absorption fine structure spectroscopy, have contributed to the elucidation of the structural biology of protein-mediated mechanisms of heavy metal homeostasis. Among the most striking aspects of these investigations are the remarkable similarity of metal-ion-transport and sequestering systems across different species, and the need to continue the research to confirm hypotheses for the molecular mechanisms of transfers of metal ions between proteins.