Cellular copper transport processes are required by all organisms for correct utilization in cell biochemical processes and avoidance of the toxicity of copper excess. Copper import into bacterial, yeast, and mammalian cells requires the coordinate function of proteins with both metal-binding and catalytic domains in mediated transport steps. Following entry, detoxification mechanisms found across species include the binding of copper to specific proteins (e.g. metallothioneins) and the transfer of copper into isolated cell compartments (e.g. periplasmic space, lysosome). Multiple proteins mediate intracellular transfers in bacteria, and glutathione may play a major role in cytosolic copper delivery to cuproenzymes in mammalian cells. Study of two human disorders of copper transport, Menkes disease and Wilson disease, led to the identification of an important category of proteins mediating cell copper export. The Menkes and Wilson disease gene products are copper-transporting ATPases of the P type, with ATPase domains and N-terminal metal-binding amino acid motifs that are evolutionarily conserved in unicellular and mammalian organisms. These observations suggest that yeast and bacterial copper transport proteins, or individual domains of these proteins, may generally have homologues in mammalian systems.