Enzymes that employ transition metals as co-factors are housed in a wide variety of intracellular locations or are exported to the extracellular milieu. A key question then arises: how are specific metal co-factors transported to diverse locations and subsequently sorted into the correct metalloenzymes? The mechanisms by which these tasks are accomplished are just now being unraveled. A new family of soluble metal receptor proteins known as “metallochaperones” is emerging that act in the intracellular trafficking of metal ions. Although transition elements can be quite toxic, these metal receptors are not detoxification proteins; they clearly function in a “chaperonelike” manner, guiding and protecting the metal ion while facilitating appropriate partnerships. Here we will review the most recent advances in our understanding of copper metallochaperones and discuss mechanisms that may be relevant to other essential, yet potentially toxic, metal ions.