This review discusses the role of copper in biology, focusing on its various active sites and mechanisms in copper enzymes. Copper plays a key role in electron transfer, oxygen activation, and substrate activation. The review highlights two main types of copper sites: the mononuclear blue Cu site, which has a highly covalent Cu²⁺-S(Cys) bond, and the binuclear CuA site, which has a Cu₂S(Cys)₂ core with a Cu-Cu bond that keeps the site delocalized. These sites are crucial for intramolecular electron transfer in multi-center enzymes. The review also discusses the role of copper in oxygen activation and reduction, which often involves multiple copper centers or redox active organic cofactors. The review covers various classes of copper enzymes, including oxidases that catalyze the four-electron reduction of O₂ to H₂O, and enzymes involved in nitrite and nitrous oxide reduction. The review also discusses the electronic structure and spectroscopy of copper sites, including X-ray absorption spectroscopy (XAS), electron paramagnetic resonance (EPR), and X-ray magnetic circular dichroism (XMCD). The review highlights the importance of ligand field theory in understanding the electronic structure of copper sites and the role of covalency in activating substrates for spin-forbidden reactions with O₂. The review also discusses the role of copper in bacterial denitrification and the activation of covalently bound substrates by oxidized Cu(II) centers. The review concludes with a discussion of the application of various spectroscopic methods to study copper enzymes and their electronic structures.This review discusses the role of copper in biology, focusing on its various active sites and mechanisms in copper enzymes. Copper plays a key role in electron transfer, oxygen activation, and substrate activation. The review highlights two main types of copper sites: the mononuclear blue Cu site, which has a highly covalent Cu²⁺-S(Cys) bond, and the binuclear CuA site, which has a Cu₂S(Cys)₂ core with a Cu-Cu bond that keeps the site delocalized. These sites are crucial for intramolecular electron transfer in multi-center enzymes. The review also discusses the role of copper in oxygen activation and reduction, which often involves multiple copper centers or redox active organic cofactors. The review covers various classes of copper enzymes, including oxidases that catalyze the four-electron reduction of O₂ to H₂O, and enzymes involved in nitrite and nitrous oxide reduction. The review also discusses the electronic structure and spectroscopy of copper sites, including X-ray absorption spectroscopy (XAS), electron paramagnetic resonance (EPR), and X-ray magnetic circular dichroism (XMCD). The review highlights the importance of ligand field theory in understanding the electronic structure of copper sites and the role of covalency in activating substrates for spin-forbidden reactions with O₂. The review also discusses the role of copper in bacterial denitrification and the activation of covalently bound substrates by oxidized Cu(II) centers. The review concludes with a discussion of the application of various spectroscopic methods to study copper enzymes and their electronic structures.