Biological processes that fractionate Cu isotopes are not well-understood, but play an important role in driving the δCu values of materials observed in the marine and terrestrial environments. The natural Cu/Cu varies according to coppers redox form and the ligand to which copper binds. Oxidized Cu preferentially coordinates with hard donor ligands (e.g., N- or O-containing ligands), while reduced Cu preferentially coordinates with soft donor ligands (e.g., S-containing ligands). As Cu is preferentially oxidized over Cu, these isotopes tend to coordinate with hard and soft donor ligands, respectively. Cu isotopes can fractionate upon Cu-bacteria interactions from processes that include Cu adsorption to cells, intracellular uptake, metabolic regulation and redox speciation. Fractionation of Cu isotopes upon adsorption to cellular walls appears to depend on the surface functional groups that Cu complexes with, and can span positive and negative values. Furthermore, bacteria preferentially incorporate the lighter Cu isotope intracellularly and into proteins. For example, E. coli, B. subtilis and a natural consortia of microbes sequestered Cu with apparent fractionations (εCu) ranging from ~-1.0 to -4.4‰. Additionally, fractionation of Cu upon incorporation into the apoprotein of azurin was ~-1‰ in P. aeruginosa, and -1.5‰ in E. coli', while εCu values of Cu incorporation into Cu-metallothionein and Cu-Zn-SOD in yeast were -1.7 and -1.2‰, respectively.