The Cu,ZnSODs (Cu,Zn superoxide dismutases) comprise a class of ubiquitous metalloenzymes that catalyse the dismutation of the superoxide radical anion into oxygen and hydrogen peroxide. The dismutation reaction involves two successive encounters of the superoxide anion with a catalytic copper centre hosted by the enzyme at the dead end of a narrow protein channel. Cu,ZnSOD is found in all eukaryotic species as a homodimeric enzyme of approx. 2×16 kDa. Cu,ZnSODs are also widely distributed in the prokaryotic phyla, and are found in the periplasmic space of bacterial pathogens, where they are likely to play a defensive role against extracellular oxidative stress, particularly with respect to phagocytic processes. The crystallographic structures of prokaryotic Cu,ZnSODs have shown that the core structural organization of the enzyme is based on a flattened antiparallel β-barrel, composed of eight strands arranged in a Greek-key topological order, which usually forms a dimeric structure through the interaction of residues provided by β-strands 4f and 5e with the 2,3 and 7,8 loops. The interface residues are arranged to form a closed ring, which surrounds a central cavity filled by water molecules that are arranged differently depending on the species. The interface variability of residues and solvent structure observed in bacterial enzymes permits fine tuning of the subunit association that results in the presence of monomeric and dimeric species, and confers a particular protein flexibility that gives rise to long-range communications between different region of the enzyme.