Copper is an element that is both essential and toxic. It is a required micronutrient for energy production in aerobic eukaryotes, from unicellular yeast to plants and mammals. Copper is also required for the acquisition and systemic distribution of the essential metal iron, and so copper deficiency results in iron deficiency. Copper enzymes have been identified that explain the wide variety of symptoms suffered by copper deficient subjects. The cloning of the genes encoding transport proteins responsible for copper-related Menkes and Wilson diseases inspired and coincided with the discovery of copper chaperones that stimulated the copper homeostasis field. Copper continues to be implicated in new array of proteins, notably those involved in a variety of neurodegenerative diseases. Here we will describe the cadre of important historical copper proteins and survey the major metallochaperones and transporters responsible for mobilization and sequestration of copper in yeast, mammals and plants.